Colquhounia root tablet improves diabetic kidney disease by regulating epithelial-mesenchymal transition via the PTEN/PI3K/AKT pathway.

Background: Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes mellitus that can lead to end-stage renal disease. Colquhounia root tablet (CRT) has shown therapeutic potential in treating DKD, but its efficacy and underlying mechanisms remain to be elucidated. Methods: A randomized controlled clinical trial was conducted on 61 DKD patients. The treatment group received CRT in addition to standard therapy, while the control group received standard therapy alone. Treatment efficacy and adverse events were evaluated after 3 months. Additionally, in vitro experiments using human renal tubular epithelial cells (HK-2) were performed to investigate the effect of CRT on high glucose (HG)-induced epithelial-mesenchymal transition (EMT) and the involvement of the PTEN/PI3K/AKT signaling pathway. Results: CRT treatment significantly improved proteinuria and increased the effective treatment rate in DKD patients compared to the control group, with no significant difference in adverse events. Moreover, CRT reversed HG-induced EMT in HK-2 cells, as evidenced by the downregulation of α-SMA and upregulation of E-cadherin at both mRNA and protein levels. Mechanistically, CRT increased PTEN expression and inhibited the PI3K/AKT pathway, similar to the effects of the PI3K inhibitor LY29400. The combination of CRT and LY29400 further enhanced PTEN mRNA expression under HG conditions. Conclusion: CRT effectively improves proteinuria in DKD patients and ameliorates HG-induced EMT in HK-2 cells. The underlying mechanism may involve the upregulation of PTEN and subsequent inhibition of the PI3K/AKT signaling pathway. These findings provide new insights into the therapeutic potential of CRT for DKD treatment.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Physiological and biochemical response of P. fortunei to Mn exposure.

Fast-growing woody plants with metal tolerance are considered as potential candidates for phytoremediation. P. fortunei is widely distributed in China. Herein, the Mn tolerance ability and physiological and biochemical response of P. fortunei to Mn were explored in this study. Results showed that a low concentration of Mn exposure was favorable for the growth of P. fortunei, while it was inhibited in high Mn exposure. P. fortunei showed high tolerance to Mn (10 mmol/L). The microstructure of P. fortunei organs revealed that the Mn tolerance of P. fortunei was related to the compartmentalization of the cell wall. The subcellular distribution of Mn in P. fortunei showed that Mn was mainly stored in the cell wall fraction (39%-90%). Under Mn exposure, the proportion of pectate and protein-integrated Mn increased by 5%-29% in P. fortunei. The changes of function groups (-CH3 and -COOH) in P. fortunei might be related to the reduction of Mn toxicity in plant cells in the way of chelation. Additionally, P. fortunei leaves resisted Mn toxicity by increasing the activities of CAT and SOD under low Mn concentration exposure, but it might be destroyed under excessive Mn concentration exposure. P. fortunei might be used as a candidate plant for low concentration Mn tailing restoration.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Resultados sensoriales y motores en pacientes miopes tratados con técnicas de superficies / Sensory and Motor Outcomes in Myopic Patients Treated with Surface Techniques

Objetivo: Evaluar los resultados sensoriales y motores poscirugía refractiva con técnicas de superficie (LASEK-MMC o PRK-MMC) en pacientes miopes con o sin astigmatismo asociado. Método: Se realizó estudio experimental controlado aleatorizado abierto, en el cual fueron incluidos 160 pacientes (320 ojos), de ellos tratados con LASEK-MMC (80 pacientes) y con PRK-MMC (80 pacientes), seguidos por 3 meses. Las principales variables evaluadas fueron: edad, tipo de error refractivo, equivalente esférico, ángulo Kappa, anisometropía, estereopsis, punto próximo de convergencia y su anomalía, amplitud de convergencia y de divergencia (cerca y lejos) y magnitud de la desviación del alineamiento ocular. Resultados: El grupo tratado con PRK-MMC tenía edad media de 26,48 años ± 4,47 y equivalente esférico preoperatorio de -3,27 ±1,54 que disminuyó significativamente (p <0,05) a -0,04 ± 0,23 dioptrías (D) a los tres meses de la cirugía. El grupo tratado con LASEK-MMC tenía edad media de 26,31 años ± 4,86 y equivalente esférico preoperatorio de -3,34 ± 1,66 dioptrías (D) que disminuyó significativamente (p <0,05) a -0,06 ± 0,26 D a los tres meses de la cirugía. Además, disminuyó la anisometropía, mejoró la estereopsis y disminuyó la amplitud la amplitud de convergencia y divergencia para lejos. El alineamiento ocular también mejoró. Conclusiones: Las técnicas de superficies para tratar pacientes con miopía o astigmatismo miópico compuesto disminuyen la anisometropía, mejoran la estereopsis y disminuyen la amplitud de convergencia y divergencia para lejos, con mayor proporción de pacientes con ortoforia después de la operación(AU)

Purpose : To evaluate sensory and motor outcomes after refractive surgery with surface techniques (LASEK-MMC or PRK-MMC) in myopic patients with or without associated astigmatism. Methods : An open randomized controlled experimental study was performed, in which 160 patients (320 eyes) were included, treated with LASEK-MMC (80 patients) and with PRK-MMC (80 patients), followed up during 3 months. The main variables evaluated were: age, type of refractive error, spherical equivalent, Kappa angle, anisometropia, stereopsis, near convergence point and its anomaly, convergence and divergence amplitude (near and far) and magnitude of ocular alignment deviation. Results : The group treated with PRK-MMC had an average age of 26.48 years ± 4.47 and preoperative spherical equivalent of -3.27 ± 1.54 which decreased significantly (p < 0.05) to -0.04 ± 0.23 diopters (D) three months after surgery. The LASEK-MMC treated group had an average age of 26.31 years ± 4.86 and preoperative spherical equivalent of -3.34 ± 1.66 diopters (D) which decreased significantly (p < 0.05) to -0.06 ± 0.26 D three months after surgery. In addition, anisometropia decreased, stereopsis improved, Kappa angle increased, and convergence and divergence amplitude (for far) decreased; ocular alignment also improved. Conclusions : Surface techniques to treat patients with myopia or compound myopic astigmatism decrease anisometropia, improve stereopsis, increase Kappa angle, and decrease near point anomaly and convergence and divergence amplitude (for far), with higher proportion of patients with orthophoria postoperatively(AU)

Complement C3a receptor inactivation attenuates retinal degeneration induced by oxidative damage.

Retinal degeneration causes vision loss and threatens the health of elderly individuals worldwide. Evidence indicates that the activation of the complement system is associated with retinal degeneration. However, the mechanism of complement signaling in retinal degeneration needs to be further studied. In this study, we show that the expression of C3 and C3a receptor (C3ar1) is positively associated with the inflammatory response and retinal degeneration. Genetic deletion of C3 and pharmacological inhibition of C3ar1 resulted in the alleviation of neuroinflammation, prevention of photoreceptor cell apoptosis and restoration of visual function. RNA sequencing (RNA-seq) identified a C3ar1-dependent network shown to regulate microglial activation and astrocyte gliosis formation. Mechanistically, we found that STAT3 functioned downstream of the C3-C3ar1 pathway and that the C3ar1-STAT3 pathway functionally mediated the immune response and photoreceptor cell degeneration in response to oxidative stress. These findings reveal an important role of C3ar1 in oxidative-induced retinal degeneration and suggest that intervention of the C3ar1 pathway may alleviate retinal degeneration.

Sensibilidad al contraste y aberrometría ocular en pacientes operados de miopía con técnicas de superficie / Contrast Sensitivity and Ocular Aberrometry in Patients Operated on for Myopia with Surface Techniques

Objetivo: Determinar el cambio de la sensibilidad al contraste en pacientes operados de miopía con técnicas de superficie y su relación con la aberrometría ocular. Métodos: Se realizó un estudio experimental con 324 ojos de 162 pacientes miopes atendidos en la consulta de Cirugía Refractiva del Instituto Cubano de Oftalmología "Ramón Pando Ferrer" en el período de enero 2019 y marzo de 2020 y que fueron operados de cirugía refractiva con láser de excímero, técnicas de superficie y perfil de ablación asférico. La sensibilidad al contraste fue la variable principal de comparación entre ambas técnicas quirúrgicas. Se formaron dos grupos de pacientes, cuya asignación fue secuencial, al primer grupo, se le realizó la técnica quirúrgica PRK-MMC (81) y al segundo LASEK-MMC (81) con un seguimiento de 3 meses. Resultados: Predominaron las mujeres con miopía leve y edades entre 21 y 28 años. A los tres meses la sensibilidad al contraste, agudeza visual sin corrección, equivalente esférico y el valor cuadrático medio total mejoraron de manera significativa, mostrando una relación positiva con la sensibilidad al contraste en ambos grupos, sin diferencias entre ellos. Conclusiones: La sensibilidad al contraste mejora con técnicas de superficie y posee una relación positiva y significativa con los resultados visuales, refractivos y aberrométricos. El estudio de las aberraciones oculares proporciona un arma fundamental para valorar la calidad óptica del ojo humano, información que permite conocer la calidad visual que se puede esperar en los pacientes evaluados(AU)

Objective: To determine the change in contrast sensitivity in patients operated on for myopia with surface techniques and its relationship with ocular aberrometry. Methods: An experimental study was carried out with 324 eyes of 162 myopic patients treated at the Refractive Surgery Clinic of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer" between January 2019 and March 2020 who underwent refractive surgery with excimer laser and surface techniques and aspheric ablation profile. Contrast sensitivity was the main variable of comparison between both surgical techniques. Two groups of patients were sequentially assigned, the first group underwent PRK-MMC (81) and the second LASEK-MMC (81) with a 3-month follow-up. Results: Women with mild myopia and ages between 21 and 28 years predominated. After 3 months contrast sensitivity, uncorrected visual acuity, spherical equivalent and total average square value improved significantly, showing a positive relationship with contrast sensitivity in both groups, with no differences between them. Conclusions: Contrast sensitivity improves with surface techniques and has a positive and significant relationship with visual, refractive and aberrometric outcomes. The study of ocular aberrations provides a fundamental tool to assess the optical quality of the human eye, information that allows us to know the vision quality that can be expected in the patients evaluated(AU)

Complement C3 deficiency alleviates alkylation-induced retinal degeneration in mice.

BACKGROUND: It has been found that the extensive use of anticancer drugs containing DNA-alkylating agents not only target cancer cells but also cause retinal inflammation through toxic intermediates. Complement C3 (C3) is a core component of the complement activation pathway, and dysregulation of the complement pathway is involved in several retinal degenerative diseases. However, whether C3 plays a critical role in alkylation-induced retinal degeneration is unclear. METHODS: Following treatment with the alkylating agent methyl methane sulfonate (MMS), the C3 mRNA and protein level was measured, DNA damage and photoreceptor cell death were assessed in both wild-type (WT) C57BL/6J and C3 knockout (KO) mice. RESULTS: We determined that complement pathway is activated following MMS treatment, and C3 knockout (KO) increased the rate of photoreceptor cell survival and preserved visual function. The mRNA levels of nuclear erythroid-related factor 2 (Nrf2) and related genes were higher after MMS application in C3 KO mice. CONCLUSION: In summary, our study found that C3 KO promotes photoreceptor cell survival and activates the Nrf2 signaling pathway in the context of alkylation-induced retinal degeneration.

Integration of manganese accumulation, subcellular distribution, chemical forms, and physiological responses to understand manganese tolerance in Macleaya cordata.

Macleaya cordata (Willd.) R. Br. are proposed for the application in phytoremediation of heavy metal-contaminated soil. In this paper, the physiological response, subcellular distribution, chemical form, ultrastructure, and manganese (Mn) absorption characteristics of M. cordata under the stress of 0, 3, 6, 9, 12, and 15 mmol/L manganese concentration were studied by sand culture experiment. The results showed that M. cordata seedlings show high tolerance to Mn stress with a concentration of less than 6 mmol/L, while higher Mn concentration showed a significant toxic effect. A low concentration of Mn (≤ 6 mmol/L) can promote the synthesis of chlorophyll and soluble protein; furthermore, superoxide dismutase and peroxidase activities responded positively. The accumulation of Mn in the inactive metabolic part (cell wall and vacuole) of M. cordata leaves might be one of the main Mn detoxification mechanism. According to the ultrastructure of M. cordata, high-concentration Mn2+ (≥ 12 mmol/L) stress can cause M. cordata cells to be distorted and deformed, black precipitates appeared in the intercellular space, mitochondria decrease, chloroplasts shrink, hungry particles increased, and starch granules decrease. The uptake ability of different tissues for Mn is leaf > root > stem, and transport coefficient decreases with the increase of Mn concentration. Clearly, M. cordata has a certain tolerance to manganese, which has the ecological application potential in Mn-polluted areas.

Ocular manifestations of multiple sclerosis in patients from three countries: A Web-based survey.

OBJECTIVE: This study evaluates the epidemiological characteristics, ophthalmological manifestations, and different therapeutic options available for patients with multiple sclerosis (MS) in China, Spain, and Cuba. METHODS: A self-designed questionnaire was used to conduct a comparable descriptive cross-sectional study on patients with MS. The survey included patients' demographic data, ocular manifestations related to MS, and treatment methodology followed in the three countries. The online survey was designed using the Wenjuanxing survey platform, and a survey link was circulated through WhatsApp, WeChat, and emails. Quantitative data were expressed as mean and standard deviation, the Kruskal-Wallis test was used for non-parametric variables. Qualitative data were expressed as numerical and percentage. The chi-square test (χ2) was used to compare the group's response categories. The statistical difference was considered significant when p < 0.05. RESULTS: The female-to-male ratio in all the three countries was 2-3:1, and relapsing-remitting MS (RRMS) was the most frequent in all three countries. Vision loss was slow and progressive in half of the patients from the three countries, with no significant differences (p = 0.524). A higher percentage of steroid treatment was observed in Chinese patients in comparison with the patients from other two countries (p < 0.001), and a similar trend was seen in the use of traditional medicines. Almost one-third of patients who did not receive any treatment recovered spontaneously in all the three countries (p = 0.097). CONCLUSIONS: MS occurs more frequently in the relapsing-remitting clinical form and there is a clear female predominance. The first ocular crisis or clinical debut of MS is characterized by slow and progressive visual impairment, increasing and adding to other ocular manifestations during its evolutionary course. Spontaneous recovery of vision after an attack of optic neuritis in the course of MS is possible.

Resultados refractivos y visuales en pacientes operados de miopía con técnicas de superficies / Refractive and visual results in patients operated on for myopia with surface techniques

Objetivo: Comparar los resultados visuales y refractivos pre- y posoperatorios en pacientes miopes operados con técnicas de superficie y perfil de ablación asférico. Métodos: Se realizó un estudio experimental controlado aleatorizado abierto, tipo de equivalencia y no inferioridad, en 160 pacientes (320 ojos). En el estudio se formaron dos grupos: el primero quedó constituido por 80 pacientes (160 ojos), a quienes se les realizó queratectomía fotorrefractiva más mitomicina C, y el segundo fue conformado por 80 pacientes (160 ojos), a quienes se les realizó LASEK más mitomicina C. Resultados: Predominaron en ambos grupos las mujeres con miopía leve y edades entre 21 y 29 años. A los tres meses el grupo queratectomía fotorrefractiva más mitomicina C tenía agudeza visual sin corrección de 0,97 ± 0,09; esfera 0,003 ± 0,21; cilindro -0,09 ± 0,30 y equivalente esférico -0,04 ± 0,23. En el grupo LASEK más mitomicina C, la agudeza visual sin corrección fue de 0,96 ± 0,11; la esfera -0,007 ± 0,24; el cilindro -0,08 ± 0,25 y el equivalente esférico -0,06 ± 0,26. Conclusión: Ambas técnicas quirúrgicas mejoraron significativamente los resultados refractivos y visuales, pero no hubo diferencia entre ellas(AU)

Objective: Compare the pre- and postoperative visual and refractive results in myopic patients operated with surface techniques and aspheric ablation profile. Methods: An open randomized controlled experimental study, equivalence and non-inferiority type was carried out in 160 patients (320 eyes). In the study, two groups were formed: the first group was made up of 80 patients (160 eyes), who underwent Photorefractive keratectomy - mitomycin C, and the second group made up of 80 patients (160 eyes), underwent LASEK - mitomycin C. Results: Women with mild myopia and ages between 21 and 29 years old predominated in both groups. At three months, the Photorefractive keratectomy - mitomycin C group had AVSC 0.97 ± 0.09; sphere 0.003 ± 0.21; cylinder -0.09 ± 0.30 and spherical equivalent -0.04 ± 0, 2. 3. In the Photorefractive keratectomy - mitomycin C group, AVSC 0.96 ± 0.11; sphere -0.007 ± 0.24; cylinder -0.08 ± 0.25 and spherical equivalent -0.06 ± 0.26. Conclusion: Both surgical techniques improved significantly refractive and visual results, but there was no difference between them(AU)

Factores asociados a la prevalencia de la miopía mundial y su impacto social / Factors associated to global myopia prevalence and its social impact

La miopía es una alteración visual que se encuentra entre las cinco condiciones cuya atención clínica ha sido calificada de prioridad inmediata para la Organización Mundial de la Salud. Esta afección ocular ya ha alcanzado proporciones epidémicas en todo el mundo y se estima que las cifras de prevalencia de miopía global continúen creciendo. Los adolescentes y jóvenes resultan los más afectados. Para realizar un acercamiento al tema se utilizaron metabuscadores en inglés y en español de PUBMED, INFOMED, EBSCO, SCIELO, PRISMA, y UPTODATE, con el objetivo de identificar los factores asociados, la prevalencia y el impacto social de la miopía. Los estudios revisados mostraron que mientras más temprano comience el desarrollo de este error refractivo, mayores serán las probabilidades de padecer miopía magna y complicaciones asociadas a ella con posterioridad. Múltiples factores propician su aparición, algunos de ellos totalmente evitables asociados a patrones de comportamiento y estilos de vida, por lo que teniendo en cuenta lo alarmante del incremento de la afección se hace necesario trazar estrategias que permitan frenar su aparición y/o progresión(AU)

Myopia is one the five conditions of the eye whose clinical care has been declared an immediate priority by the World Health Organization. This condition has already reached epidemic proportions worldwide, and its prevalence is expected to continue to increase in the future. Adolescents and young people are the most commonly affected groups. With the purpose of identifying the associated factors, prevalence and social impact of myopia, a search was conducted for articles about the topic published in English and Spanish in the databases PubMed, Infomed, EBSCO, SciELO, PRISMA and UpToDate. The studies retrieved showed that early development of the refractive error will result in a greater probability of suffering from myopia magna and related complications. Multiple factors may lead to the appearance of global myopia. Some of them are totally preventable, since they have to do with behavior patterns and lifestyles. Considering the alarming increase in the occurrence of this condition, it is necessary to devise strategies allowing to contain its appearance and/or progression(AU)

Diagnostic Techniques for COVID-19: A Mini-review of Early Diagnostic Methods.

The outbreak of severe pneumonia at the end of 2019 was proved to be caused by the SARS-CoV-2 virus spreading out the world. And COVID-19 spread rapidly through a terrible transmission way by human-to-human, which led to many suspected cases waiting to be diagnosed and huge daily samples needed to be tested by an effective and rapid detection method. With an increasing number of COVID-19 infections, medical pressure is severe. Therefore, more efficient and accurate diagnosis methods were keen urgently established. In this review, we summarized several methods that can rapidly and sensitively identify COVID-19; some of them are widely used as the diagnostic techniques for SARS-CoV-2 in various countries, some diagnostic technologies refer to SARS (Severe Acute Respiratory Syndrome) or/and MERS (Middle East Respiratory Syndrome) detection, which may provide potential diagnosis ideas.

Spent mushroom compost and calcium carbonate modification enhances phytoremediation potential of Macleaya cordata to lead-zinc mine tailings.

Phytoremediation is an essential technique for mines' ecological restoration. Modifiers addition can alleviate the stress of heavy metals to plants and enhanced remediation efficiency. Herein, spent mushroom compost (SMC) and calcium carbonate (CaCO3) were added to lead-zinc mine tailings to reveal the mechanism of Macleaya cordata adaptive to heavy metals stress. Pot experiments were conducted in 100% tailing (T), 90% tailing + 5% SMC + 5% CaCO3 (T+), and 100% natural soil (NS). The results indicate that SMC and CaCO3 amendments could improve the structure and fertility of tailings, and promote the growth of M. cordata, increase the content of heavy metals accumulated in plants, enhance the synthesis of chlorophyll and increas the content of soluble protein in leaves; enhance the activities of antioxidase, that can protectcelluar components from oxidative damage. Moreover, most of Pb, Zn, and Cd existed in the cell wall and soluble components, adding SMC and CaCO3 could promote the conversion of Pb, Zn, and Cd to chemical forms with less toxicity and migratory capability. The results of transmission electron microscopy (TEM) and Fourier transform infrared spectrometer (FTIR) showed that SMC and CaCO3 could protect the structural integrity of cells and increase the contents of -OH, -COOH functional groups that can bind to heavy metals in cells. The addition of SMC and CaCO3 can alleviate the stress of heavy metals on M. cordata, enhancing its adaptability to heavy metals and phytoremediation capacity.

The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Comparación de las características de la córnea entre individuos chinos y cubanos / Comparison between corneal features of Chinese and Cuban subjects

Objetivo: Comparar las características de la córnea entre individuos chinos y cubanos adultos sanos. Métodos: Se realizó un estudio observacional, descriptivo, transversal, en 120 ojos de individuos sanos (60 chinos y 60 cubanos), entre 18 y 29 años de edad, entre septiembre del año 2016 y diciembre de 2017 en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Se evaluó la edad, el sexo, la queratometría, la paquimetría y las características del endotelio corneal. Resultados: Predominó el sexo femenino (53,3 por ciento en los cubanos y 66,6 por ciento en los chinos). La edad promedio fue de 24,4 años en ambos grupos. La queratometría promedio resultó mayor en el grupo de estudio de cubanos, con un valor de 44,7 y 44,6 dioptrías en ambos ojos, respectivamente. El espesor corneal fue de 607,3-629,9 en los cubanos y de 575,4-607,2 en los chinos. El coeficiente de variación, la desviación estándar y la densidad celular se diferenciaron mínimamente en ambos ojos para ambas nacionalidades, y resultaron superiores en los ojos izquierdos con un coeficiente de 32,0 (±11,0) en los chinos. La desviación estándar promedio fue de 112,0 (± 36,5) en ambos grupos y en el ojo derecho la densidad celular fue 2 857,1 (± 240,0 cél/mm2) en los chinos y 2 760,0 (± 367,2) en los cubanos. El average de los cubanos estuvo entre 369,0 y 380, y para los chinos entre 352,4 y 358,4 en los ojos derecho e izquierdo. Conclusiones: Existen diferencias significativas en los valores queratométricos. El espesor corneal resulta discretamente más reducido en los chinos. El coeficiente de variación, la densidad celular, el average y la desviación estándar no presentan diferencias estadísticamente significativas(AU)

Objective: Compare the corneal features of Chinese and Cuban healthy adult subjects. Methods: A cross-sectional observational descriptive study was conducted of 120 eyes of healthy 18-29 year old individuals (60 Chinese and 60 Cuban) from September 2016 to December 2017 at Ramón Pando Ferrer Cuban Institute of Ophthalmology. The variables analyzed were sex, keratometry, pachymetry and characteristics of the corneal endothelium. Results: Female sex prevailed (53.3 percent among Cuban and 66.6 percent among Chinese subjects). Mean age was 24.4 years in both groups. Mean keratometry was higher in the Cuban group, with values of 44.7 and 44.6 diopters for both eyes, respectively. Corneal thickness was 607.3-629.9 among Cuban and 575.4-607.2 among Chinese subjects. Variation coefficient, standard deviation and cell density were minimally different between the two eyes in both groups, and were higher in left eyes of Chinese subjects with a coefficient of 32.0 (±11.0). Mean standard deviation was 112.0 (± 36.5) in both groups, whereas right eye cell density was 2 857.1 (± 240.0 cell/mm2) among Chinese and 2 760.0 (± 367.2) among Cuban subjects. Average between right and left eyes ranged from 369.0 to 380 for the Cubans and from 352.4 to 358.4 for the Chinese. Conclusions: Significant differences were found between keratometric values. Corneal thickness was slightly lower among Chinese subjects. Variation coefficient, cell density, average and standard deviation did not show any statistically significant differences(AU)

1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis.

NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis, Parkinson's disease, and stroke. Targeting the NLRP3 inflammasome is beneficial to these diseases, but few NLRP3 inflammasome-selective inhibitors are identified to date. Essential oils (EOs) are liquid mixtures of volatile and low molecular-weight organic compounds extracted from aromatic plants, which show various pharmacological activities, including antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory properties. In this study we screened active ingredients from essential oils, and identified 1,2,4-trimethoxybenzene (1,2,4-TTB) as a selective NLRP3 inflammasome inhibitor. We showed that 1,2,4-TTB (1 mM) markedly suppressed nigericin- or ATP-induced NLRP3 inflammasome activation, thus decreased caspase-1 activation and IL-1ß secretion in immortalized murine bone marrow-derived macrophages (iBMDMs) and in primary mouse microglia. Moreover, 1,2,4-TTB specifically inhibited the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. We further demonstrated that 1,2,4-TTB inhibited oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly in iBMDMs and in primary mouse macrophages. In mice with experimental autoimmune encephalomyelitis (EAE), administration of 1,2,4-TTB (200 mg · kg-1 · d-1, i.g. for 17 days) significantly ameliorated EAE progression and demyelination. In conclusion, our results demonstrate that 1,2,4-TTB is an NLRP3 inflammasome inhibitor and attenuates the clinical symptom and inflammation of EAE, suggesting that 1,2,4-TTB is a potential candidate compound for treating NLRP3 inflammasome-driven diseases, such as multiple sclerosis.

Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.

Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase (N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase (N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase (n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer-Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.