Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Association of serum alpha-1 antitrypsin level with the severity of COPD

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder linked to early onset COPD, notably the emphysema variety, but often goes undetected. Low serum AAT levels may impact lung function and correlate with COPD severity. The aim of the study was to detect possible associations of serum AAT level with the severity of COPD patients on the basis of post bronchodilator FEV1 in Bangabandhu Sheikh Mujib Medical University (BSMMU). Methods: A cross-sectional study was conducted at the Department of Respiratory Medicine, BSMMU, Dhaka, from October 2022 to September 2023. Adult patients (?18 years) of both genders diagnosed with COPD based on spirometry were included. COPD was defined per GOLD guidelines, with a post-bronchodilator FEV1/FVC ratio <70%. Severity was categorized based on post-bronchodilator FEV1% predicted. Association between serum AAT level and COPD severity was analyzed using SPSS version 26, with significance set at p <0.05. Results: The study involved 80 COPD patients, with 1.25% showing low serum AAT levels and 98.75% normal. No significant differences in age, sex, or smoking status were observed among severity groups. Mean serum AAT levels varied across severity groups but were not statistically significant (p=0.377). Smoking was prevalent (66.3%), with common comorbidities like hypertension (26.3%), IHD (16.3%), and diabetes mellitus (15.0%). Shortness of breath (95.0%) and cough (92.5%) were common symptoms, with most patients having moderate disease severity (42.5%). Conclusions: The study indicates a weak association between serum AAT levels and COPD severity, with only 1.25% of 80 patients exhibiting low AAT levels.

Orogenital ulcers and the Behcet’s disease

Behcet’s’s disease is a systemic vasculitis involving small to large veins and arteries. It is a sporadic disease, mostly prevalent among the ancestors of the silk route. It is characterized by recurrent oral ulcers, genital ulcers, and uveitis. It also can manifest as skin, vascular, gastrointestinal, neurological, cardiac, and renal involvement. Though overall mortality is around 5%, delay in diagnosis and treatment may lead to significant morbidity. Cardiovascular and pulmonary arterial aneurysms are dreadful complications of this disease. Being uncommon in south India it is liable to be wrongly diagnosed and treated. Delay in the diagnosis and treatment may lead to severe complications. Here we present a case of Behcet’s disease which was managed at primary health care inadequately. We also demonstrated a quick response to steroids which are the mainstay of treatment. In this case presentation we illustrated pre and post treatment scrotal and oral Behcet’s’s lesions for clinicians to memorize. We also discussed international criteria to diagnose Behcet’s disease (ICBD) in concurrence with our case. In this presentation, we briefly described the involvement of other systems and their treatment. This article also elaborated on the latest developments in the treatment of Behcet’s disease.

A meta-analysis evaluating the role of calcium channel alpha-2 delta-1 subunit in carcinogenesis

There is hardly found any study accumulating all the experiments reported with the expression of alpha-2 delta-1 (?2?-1) in cancer cells. This meta-analysis aimed to advance our knowledge about the role of calcium channel alpha2 delta-1 subunit in carcinogenesis in the present time. PubMed searches for peer-reviewed articles were conducted using the keywords “?2?-1 protein in oncogenesis”, “?2?-1 protein expression in cancer cells”, and “?2?-1 protein as cancer cell marker”. The databases were developed in accordance with PRISMA guidelines. Seventeen studies out of 80 citations met the inclusion criteria pertaining to ?2?-1 expression in different cancer cells. The cancer patterns were hepatocellular carcinoma in 41%, non-small cell lung carcinoma in 12% and laryngeal squamous cell carcinoma in 12%. The remaining studies included small-cell lung cancer (6%), gastric cancer (6%), pancreatic cancer (6%), hypopharyngeal squamous cell carcinoma (6%), breast cancer (6%) and glioblastoma multiforme (6%). ?2?-1+ cells had a higher sphere-forming and tumorigenic efficiency in 76.5% of experiments. 58.8% experiments explored mechanistically in self-renewal efficiency and tumorigenesis of ?2?-1+ cancer cells. The cancer cells expressing ?2?-1 have the potential to serve as cell surface markers for tumour-initiating cells and cancer stem cells. These intriguing findings open up a promising avenue for future research, focusing on the targeting of ?2?-1 as a potential therapeutic strategy for cancer treatment.

Do statins decrease testosterone in men? Systematic review and meta-analysis

ABSTRACT Purpose: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones. Materials and Methods: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool. Results: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001). In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal. Conclusion: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.

Clinical Effect Observation of Apatinib Combined with 131I for Radioiodine-Refractory Differentiated Thyroid Cancer and Prognostic Significance Analysis of Macrophage Inflammatory Protein-1alpha After Treatment: A Cell Regulation Study / Observación del Efecto Clínico de Apatinib Combinado con 131I para el Cáncer de Tiroides Diferenciado Resistente al Yodo Radiactivo y Análisis de Importancia Pronóstica de la Proteína Inflamatoria 1alfa de Macrófagos Después del Tratamiento: Un Estudio de Regulación Celular

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.

El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.

Dupilumab in Eosinophilic Esophagitis Refractory to Conventional Management in Pediatrics: Report of Two Cases / Dupilumab en esofagitis eosinofílica refractaria al manejo convencional en pediatría: reporte de dos casos

Abstract Introduction: This publication aims to show the clinical, endoscopic, and histological responses of two pediatric patients who received dupilumab as a management strategy for eosinophilic esophagitis. Dupilumab is a monoclonal antibody that inhibits the alpha chain of the interleukin (IL)-4 and IL-13 receptors involved in the Th2 inflammatory response. The potential therapeutic role of this biological drug has been demonstrated in pediatric clinical trials in other allergic pathologies, such as atopic dermatitis and asthma, with an adequate safety and effectiveness profile. Clinical cases: Two children with a personal history of atopy, allergic rhinitis, asthma, atopic dermatitis, and food allergy began with gastrointestinal symptoms that confirmed the diagnosis of eosinophilic esophagitis. Despite the different management strategies, adequate control of the disease was not achieved, and it is considered that they benefited from management with dupilumab due to the disease evolution and the coexistence of uncontrolled atopic dermatitis. Conclusions: In recent years, various management strategies in pediatrics have been published, particularly high-dose proton pump inhibitors, topical corticosteroids, and elimination diets. However, despite these strategies, at least one-third of patients may fail to achieve remission with initial treatment, making this entity a therapeutic challenge for the gastroenterologist and pediatric allergist. Our patients received the dose recommended for their weight and age and approved for asthma and atopic dermatitis, resulting in clinical and histological remission. The improvement in gastrointestinal symptoms was accompanied by better control of asthma, rhinitis, and dermatitis. None of the patients had adverse effects of the medication.

Resumen Introducción: El objetivo de esta publicación es mostrar la respuesta clínica, endoscópica e histológica de dos pacientes pediátricos que recibieron dupilumab como estrategia de manejo para esofagitis eosinofílica. El dupilumab es un anticuerpo monoclonal que inhibe la cadena alfa del receptor de las interleucinas 4 y 13, involucradas en la respuesta inflamatoria Th2. El potencial rol terapéutico de este medicamento biológico se ha demostrado en ensayos clínicos en pediatría en otras patologías alérgicas como la dermatitis atópica y el asma, y ha mostrado un adecuado perfil de seguridad y efectividad en pediatría. Casos clínicos: Se trata de dos niños con antecedentes personales de atopia, rinitis alérgica, asma, dermatitis atópica y alergia alimentaria, que inician con síntomas gastrointestinales que conducen a confirmar el diagnóstico de esofagitis eosinofílica, en quienes a pesar de las diferentes estrategias de manejo no se logra un adecuado control de la enfermedad, y se considera que se benefician del manejo con dupilumab por la evolución de la enfermedad, así como la coexistencia de dermatitis atópica no controlada. Conclusiones: En los últimos años se han publicado diferentes estrategias de manejo en pediatría, entre los que se destaca el uso de inhibidores de la bomba de protones a dosis altas, corticoides tópicos y las dietas de exclusión; sin embargo, a pesar de estas estrategias, al menos un tercio de los pacientes puede fallar en lograr la remisión con el manejo inicial, lo que convierte a esta entidad en un reto terapéutico para el gastroenterólogo y el alergólogo pediatra. Nuestros pacientes recibieron la dosis recomendada para su peso y edad aprobada en asma y dermatitis atópica, y se logró la remisión clínica e histológica. La mejoría de los síntomas gastrointestinales se acompañó de un mejor control del asma, la rinitis y la dermatitis. Ninguno de los pacientes tuvo efectos adversos al medicamento.

Variaciones de alfa-amilasa salival relacionadas con edad, sexo e índice de masa corporal en estudiantes universitarios / Variations of salivary alpha-amylase related to age, sex and body mass index in university students

Objetivo. Determinar la presencia y dirección de la relación entre alfa-amilasa salival (AAs), edad, sexo e índice de masa corporal (IMC) en adultos jóvenes. Métodos. Este estudio transversal se desarrolló con una muestra de 50 estudiantes de odontología de 19 a 34 años de edad, 58% mujeres y 42% hombres. Se recogieron muestras de saliva entera sin estimular en la mañana (6:30-7:30 a.m.) y en la tarde (4:00-6:00 p.m.). Los valores de AAs se determinaron mediante método cinético y se expresaron como media ± desviación estándar. Se realizaron análisis descriptivo de datos, prueba de chi-cuadrado, prueba de correlación de Pearson y prueba t de muestras pareadas. Resultados. El IMC promedio fue de 23,85 ± 3,30 kg/m2, 66% de los participantes presentó peso normal (IMC ≤ 25 kg/m2). Los niveles de AAs por la tarde (282,74 ± 59,60 U/ml) fueron mayores a los de la mañana (190,84 ± 61,80 U/ml), (t = 16,51, p < 0,0001). Los hombres mostraron niveles de AAs más altos que las mujeres (p < 0,0001). La edad no mostró asociación con los niveles de AAs. Los valores de IMC y AAs presentaron una correlación positiva (AM: r = 0,35, p = 0,0121; PM: r = 0,40, p = 0,0036). Conclusión. El nivel de actividad de AAs se puede utilizar como posible biomarcador para evaluar el IMC en relación con el sexo, especialmente en los adultos jóvenes.

Objective. To determine the presence and direction of the relationship between salivary alpha-amylase (sAA), age, sex, and body mass index (BMI) in young adults. Methods. This cross-sectional study was developed with a sample of 50 dental students from 19 to 34 years of age, 58% women and 42% men. Unstimulated whole saliva samples were collected in the morning (6:30-7:30 a.m.) and in the afternoon (4:00-6:00 p.m.). sAA values were determined by the kinetic method and expressed as mean ± standard deviation. Descriptive data analysis, chi-square test, Pearson correlation test, and paired samples t-test were made. Results. Mean BMI was 23.85 ± 3.30 kg/m2, 66% of the participants presented normal weight (BMI ≤ 25 kg/m2). Levels of sAA in the afternoon (282.74 ± 59.60 U/ml) were higher than those in the morning (190.84 ± 61.80 U/ml), (t = 16.51, p < 0, 0001). Men showed higher levels of sAA than women (p < 0.0001). Age did not show an association with sAA levels. BMI and AAs values presented a positive correlation (AM: r = 0,35, p = 0,0121; PM: r = 0,40, p = 0,0036). Conclusions. AAs activity level can be used as a potential biomarker to assess BMI in relation to sex, especially in young adults.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury

Abstract The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1β, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Alpha-1-antitrypsin level as a predictor of acute exacerbations in chronic obstructive pulmonary disease: a prospective observational study

Background: This prospective study investigated if alpha-1-antitrypsin (AAT) levels could predict chronic obstructive pulmonary disease (COPD) exacerbations needing hospitalization. Methods: 106 COPD subjects hospitalized for acute exacerbations were enrolled. Past 2-years� records were evaluated for prior exacerbation hospitalizations. AAT levels and post-stabilization FEV1 were assessed during current hospitalization. Exacerbation frequency correlated to current AAT levels and lung function. Results: Significant inverse association found between AAT levels and hospitalized exacerbations, indicating utility as a predictive biomarker for COPD patients prone to recurrent severe flares requiring admission. Patients with lower AAT levels also exhibited poorer lung function per lower FEV1 values. Conclusions: Monitoring AAT levels may promote timely interventions in high risk individuals susceptible to relapsing catastrophic exacerbations needing inpatient care. Further research warranted to validate findings and explore if supplementing deficient AAT reduces exacerbation frequency, thereby improving prognosis in this debilitating disease.

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Effect of low concentration of sodium fluoride on osteogenic/odontogenic differentiation of human dental pulp cells / 口腔疾病防治

Objective@#To study the effect of low concentrations of sodium fluoride on the osteogenic/odontogenic differentiation of human dental pulp cells (hDPCs) in vitro.@*Methods@#This study was reviewed and approved by the Ethics Committee. hDPCs were cultured using a modified tissue explant technique in vitro. The effects of different concentrations of sodium fluoride on the proliferation of hDPCs were measured by methylthiazol tetrazolium (MTT) assay. Appropriate concentrations were added to the osteogenic/odontogenic differentiation induction medium, and the cells were induced in vitro. Alizarin red S staining was used to detect the osteoblastic/odontogenic differentiation ability of the cells, and the mRNA expression of the key differentiation factors was detected by RT-qPCR. Moreover, the expression of key molecules of endoplasmic reticulum stress (ERS) was detected by RT-qPCR and Western blot. The data were analyzed with the SPSS 18.0 software package.@*Results@#Low concentration of NaF (0.1 mmol/L) could stimulate cell proliferation in vitro, while a high concentration (5-10 mmol/L) could inhibit cell proliferation (P<0.05). According to the literature and the experimental data, 0.1 mmol/L NaF was selected as the following experimental concentration. The levels of alizarin red S staining were increased after NaF induction of mixed osteogenic/odontogenic differentiation in vitro. The mRNA expression levels of key molecules for osteogenic/odontogenic differentiation, dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteocalcin (OCN), were increased (P<0.05). The mRNA levels of ERS markers (splicing x-box binding protein-1 (sXBP1), glucose-regulated protein 78 (GRP78) and activating transcription Factor 4 (ATF4) were increased in NaF-treated cells. The protein expression levels of key ER stress molecules (phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-PERK), phosphorylated eukaryotic initiation factor-2α (p-eIF2α) and ATF4) were higher in NaF-treated cells.@*Conclusion@#A low concentration of NaF promotes the osteogenic/odontogenic differentiation of hDPCs and increases the level of ER stress.

Protective effect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection / 世界急诊医学杂志（英文）

@#BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that causes bacterial pneumonia. However, with increasing bacterial resistance, there is an urgent need to develop new drugs to treat S. pneumoniae infections. Nanodefensin with a 14-carbon saturated fatty acid (ND-C14) is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of human α-defensin 5 (HD5) via an amide bond. However, it is unclear whether ND-C14 is effective against lung infections caused by S. pneumoniae. METHODS: In vitro, three groups were established, including the control group, and the HD5 and ND-C14 treatment groups. A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S. pneumoniae. The morphological changes of S. pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy. In vivo, mice were divided into sham, vehicle, and ND-C14 treatment groups. Mice in the sham group were treated with 25 µL of phosphate-buffered saline (PBS). Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25 µL of bacterial suspension with 2×108 CFU/mL (total bacterial count: 5×106 CFU), and then the mice were given 25 μL PBS or intratracheally injected with 25 μL of ND-C14 (including 20 µg or 50 µg), respectively. Survival rates were evaluated in the vehicle and ND-C14 treatment groups. Bacterial burden in the blood and bronchoalveolar lavage fluid were counted. The lung histology of the mice was assessed. A propidium iodide uptake assay was used to clarify the destructive effect of ND-C14 against S. pneumoniae. RESULTS: Compared with HD5, ND-C14 had a better bactericidal effect against S. pneumoniae because of its stronger ability to destroy the membrane structure of S. pneumoniae in vitro. In vivo, ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S. pneumoniae. ND-C14 reduced bacterial burden and lung tissue injury. Moreover, ND-C14 had a membrane permeation effect on S. pneumoniae, and its destructive ability increased with increasing ND-C14 concentration.

Development and verification of a rapid detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line / 中国生物制品学杂志

@#Objective To develop and verify a rapid detection method for the biological activity of adalimumab based on U937-NF-κB-Luc cell line. Methods Using U937-NF-κB-Luc cell line as the detection cells,a method for detecting the biological activity of adalimumab was developed based on luciferase luminescence principle. The method was optimized for the concentration of tumor necrosis factor-α(TNF-α)(160 ng/mL as initial concentration,2 times serial dilution,10dilutions),the initial concentration of antibody(2 000 ng/mL,2 times serial dilution,20 dilutions),the dilution multiple of antibody(1. 5,2,3,4 times),the inoculation amount(8 × 103,2 × 104,4 × 104,6 × 104cells/well)and the incubation time(0. 5,1,2,3 h),and verified for the specificity,accuracy,precision and linear range. The relative potency of five batches of adalimumab was detected by using the optimized method and TNF-α neutralization activity method based on L929cells respectively. Results The dose-response curve of adalimumab international standard showed a typical S-type,and the data complied with the four-parameter equation y =(A-D)/[1 +(x/C)B]+ D,R2> 0. 99. The optimum concentration of TNF-α was 5 ng/mL,the initial concentration of antibody was 800 ng/mL,the dilution ratio for adalimumab was 1∶2,the inoculation amount was 2 × 104cells/well,and the induction time was 2 h. Three therapeutic monoclonal antibodies of TNF-α target,such as adalimumab,obtained good dose-response curves,while therapeutic monoclonal antibodies of other non-TNF-α targets did not show this curve. The linear regression equation of the logarithmic value of theoretical potency and the logarithmic value of the corresponding measured potency had a slope of 1. 037,and the relative bias was within the range of ± 12%. The geometric coefficient of variation(GCV)of the relative titer measured value of each sample was less than20%. The theoretical potency ranged from 64% to 156%,showing a good linear relationship with the measured values,and the fitting linear regression equation was y = 1. 037 4 x-0. 023 7,R2= 0. 998 4. There was no significant difference in the relative potency measured results of five batches of adalimumab by the two methods(t = 1. 198,P = 0. 265 1). Conclusion The developed detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line has good specificity,accuracy and precision with short time consumption(3 h),which can be used as a rapid evaluation method for the biological activity of adalimumab.

Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b / 临床肝胆病杂志

ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.

Application of alpha-fetoprotein and IL-6 in prognostic prediction of patients with hepatitis B related liver failure / 公共卫生与预防医学

Objective To analyze the application value of alpha-fetoprotein (AFP) and interleukin-6 (IL-6) in prognosis prediction of hepatitis B virus (HBV) associated liver failure. Methods A total of 135 patients with HBV-related liver failure who underwent treatment at the Infection Department of the Second People's Hospital of Yibin City from July 2020 to June 2022 were selected as the study subjects (observation group). Additionally, 100 patients who underwent physical examination in the hospital during the same period with normal indicators were selected as the control group. Serum levels of AFP and IL-6 were compared between the two groups. Factors influencing the prognosis of HBV-related liver failure were analyzed. Multiple logistic regression was used to analyze the risk factors affecting the prognosis of HBV-related liver failure patients. Results The levels of serum AFP and IL-6 in the control group were lower than those in the control group, and the difference was statistically significant (P10.0 pg/mL were risk factors affecting the prognosis of HBV-related liver failure. Conclusion Serum AFP and IL-6 can predict the prognosis of patients with HBV-related liver failure, which is worthy of clinical study.

The value of GNB4 and Riplet gene methylation detection in the diagnosis of primary liver cancer / 安徽医科大学学报

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Establishment and validation of nomogram of cancer specific survival of patients with hepatocellular carcinoma with negative alpha fetoprotein based on SEER Database / 吉林大学学报(医学版)

Objective:To discuss the factors related to the prognosis in the alpha fetoprotein(AFP)negative hepatocellular carcinoma(HCC)patients,and to construct the nomogram for predicting the survival time of the patients.Methods:The retrospective analysis on data of 2 064 cases of AFP negative HCC patients extracted from the Surveillance,Epidemiology,and End Results(SEER)Database was conducted,and all the patients were divided into training cohort and internal validation cohort at a ratio of 7∶3,and 101 AFP negative HCC patients from the Integrated Traditional Chinese and Western Medicine Hospital in Hunan Province were regarded as the external validation cohort.The univariate Cox regression analysis results were incorporated into the multivariate analysis,and the independent risk factors for the AFP negative HCC patients were obtained by multivariate Cox analysis to build a cancer specific survival(CSS)prognosis nomogram for the AFP negative HCC patients.The predictive efficacy and clinical utility of the nomogram were evaluated by time-dependent receiver operating characteristic curve(ROC),calibration plots,and decision curve analysis(DCA).The total score obtained from the nomogram was used for the risk stratification to compare the degree of risk discrimination between the nomogram and the American Joint Committee on Cancer(AJCC)staging system.Results:Ten independent risk factors were selected by multivariate Cox regression analysis to construct 3-year,4-year,and 5-year CSS prognostic nomograms for the AFP negative HCC patients,including the patient's age,pathological grade,surgical status,radiotherapy status,chemotherapy status,lung metastasis status,tumor size,tumor T stage,tumor M stage,and marital status.The area under curve(AUC)for the 3-year,4-year,and 5-year time-dependent ROC in the training cohort were 0.807(95%CI:0.786-0.828),0.804(95%CI:0.782-0.826),and 0.813(95%CI:0.790-0.835),respectively.In the internal validation cohort,they were 0.776(95%CI:0.743-0.810),0.772(95%CI:0.737-0.808),and 0.789(95%CI:0.752-0.826),and in the external validation cohort,they were 0.773(95%CI:0.677-0.868),0.746(95%CI:0.620-0.872),and 0.736(95%CI:0.577-0.895).The calibration plots verified that the nomogram fitted well with the perfect line.The DCA curve revealed that the net benefit of the nomogram was significatly higer than that of the AJCC staging system at certain probability thresholds compared with AJCC staging,the nomogram had a better ability to identify high-risk individuals.Conclusion:The serum AFP expression is one of the prognostic markers for the HCC patients.For those patients with AFP negative expression in serum,different considerations should be taken.The nomogram model based on multiple risk factors is a promising clinical tool for assessing the CSS in the AFP negative HCC patients.

Analysis of cytokines level in patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis / 白血病·淋巴瘤

Objective:To investigate the level change of cytokines in patients with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH).Methods:A retrospective case control study was conducted. The clinical data of 65 patients with EBV-HLH, 30 patients with infectious mononucleosis (IM) (IM group) and 40 patients with non-EBV infection-associated hemophagocytic lymphohistiocytosis (non-EBV-HLH group) who admitted to Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from February 2022 to February 2023 were retrospectively analyzed. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of the interleukin (IL)-6, IL-2, IL-10, IL-8, IL-1β, tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in serum samples of patients in the above 3 groups. The cytokines levels in EBV-HLH group were compared with those in IM group and non-EBV-HLH group, respectively.Results:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α and IFN-γ in EBV-HLH group were higher than those in the non-EBV-HLH group, and the differences were statistically significant (all P < 0.05). The cytokines levels of IL-2, IL-10 and IFN-γ in EBV-HLH group were higher than those in IM group, and the differences were statistically significant (all P < 0.05). Conclusions:The cytokines levels of IL-6, IL-2, IL-10, IL-8, IL-1β, TNF-α, IFN-γ are increased in EBV-HLH patients, which may play an important role in the development and progression of EBV-HLH.

Correlation between the Expression of Serum Elabela,LRG1 Levels and Disease Activity Index in Patients with Ulcerative Colitis / 现代检验医学杂志

Objective To investigate the expression of serum Elabela and leucine-rich-alpha-2-glycoprotein-1(LRG1)in ulcerative colitis(UC)patients and their correlation with disease activity index(DAI).Methods A total of 98 patients with UC admitted to Yuncheng Central Hospital from January to December 2022 were selected as the UC group,including 62 patients in active stage and 36 patients in remission stage.According to the severity of the disease,these patients were divided into mild group(n=26),moderate group(n=43)and severe group(n=29).In addition,these patients were grouped into gradeⅠ group(n=25),grade Ⅱ group(n=40)and grade Ⅲ group(n=33)based on the endoscopic activity index(EAI).According to the mucosal healing condition under endoscopy,these patients were divided into the healed group(n=65)and the unhealed group(n=33).Another 51 patients with colonic polyps were selected as control group 1,and 50 healthy individuals were selected as control group 2.Serum Elabela and LRG1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Pearson method was used to analyze the correlation between serum Elabela,LRG1 levels and DAI in UC patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum Elabela and LRG1 for endoscopic mucosal healing.Results The levels of Elabela(4.77±1.36 ng/ml)and LRG1(352.12±39.45 ng/ml)in UC group were higher than those in control group 1(2.51±0.53 ng/ml,121.02±21.06 ng/ml)and control group 2(2.35±0.42 ng/ml,120.35±23.49 ng/ml),and the differences were statistically significant(t= 11.410～39.000,all P＜0.05).The levels of Elabela(5.26±0.54 ng/ml)and LRG1(370.42±12.49 ng/ml)in the active group were higher than those in the remission group(3.93±0.42 ng/ml,320.60±8.47 ng/ml),and the differences were statistically significant(t=12.705,21.242,all P＜0.05).The levels of Elabela(5.89±0.20 ng/ml)and LRG1(369.92±16.59 ng/ml)in the severe group were higher than those in the moderate groups(4.51±0.67 ng/ml,356.12±18.75 ng/ml)and mild groups(3.95±0.21 ng/ml,325.65±10.14 ng/ml),and the differences were statistically significant(t=3.205～35.077,all P＜0.05).The levels of Elabela(5.80±0.18 ng/ml)and LRG1(369.16±13.47 ng/ml)in grade Ⅲ group were higher than those in grade Ⅱ group(4.49±0.35 ng/ml,355.46±16.34 ng/ml)and grade Ⅰgroup(3.86±0.16 ng/ml,324.15±8.71 ng/ml),and the differences were statistically significant(t= 3.854～48.725,all P＜0.05).The levels of Elabela(5.12±0.42 ng/ml)and LRG1(367.12±14.27 ng/ml)in unhealed group were higher than those in healed group(4.08±0.37 ng/ml,322.57±10.35 ng/ml),and the differences were statistically significant(t=12.043,15.917,all P＜0.05).The serum levels of Elabela and LRG1 in UC patients were positively correlated with EAI and ESR(r=0.602,0.298;0.576,0.302,all P＜0.05),but negatively correlated with hemoglobin level(r=-0.351,-0.334,all P＜0.05).The area under the curve predicted by the combination of serum Elabela and LRG1 for endoscopic mucosal healing was 0.926(95%CI:0.880～0.958),was higher than the 0.803(95%CI:0.741～0.856)and 0.783(95%CI:0.720～0.838)predicted by Elabela and LRG1 alone,and the difference was statistically significant(Z=4.101,4.228,all P＜0.05).Conclusion The serum levels of Elabela and LRG1 in UC patients increased,and they were related to the increase of DAI and worsening of the condition.Testing serum Elabela and LRG1 can provide a reference for evaluating mucosal healing under UC endoscopy.