Acute sarcoidosis Löfgren Syndrome treated by Chinese medicinal formula based on Syndrome Differentiation: a case - based review / Tratamiento de síndrome de Löfgren de sarcoidosis con fórmula medicinal china basada en diferenciación de síndrome: una revisión basada en casos

Löfgren syndrome (LS) is a unique acute manifestation of sarcoidosis and characterized by erythema nodosum, bilateral hilar lymphadenectasis, and/or bilateral ankle arthritis or periarthritis. A 37 - year - old female patient with LS presented with fever accompanied by multiple joint swelling and pain, nodular skin erythema, and bilateral hilar lymphadenectasis. The patient had received treatment involving non - steroidal anti - inflammatory drugs and glucocorticoids in other hospitals, but the effects were poor, and the conditions reemerged. The LS duration has lasted for more than 3 months. Following traditional Chinese medicine (TCM) treatment, syndrome differentiation as well as giving patients oral Chinese medicine decoction, the symptoms of the patient were rapidly relieved within one week and did not recur during a six - month follow - up period. This case is the first clinical report of acute sarcoidosis LS treated using T CM and reflects the significant advantages of this form of therapy in emergency treatment

El síndrome de Löfgren (LS) es una manifest ación única y aguda de sarcoidosis, caracterizada por eritrema nodoso, linfadenectasis hilar bilateral, y/o a r tritis de tobillo bilateral o periartritis. Una paciente de 37 años de sexo femenino con LS se presentó con fiebre, acompañada de inflamación y do lor múltiple de articulaciones, eritrema nodular cutáneo, y linfadenectasis hilar bilateral. La paciente recibió un tratamiento que consistió en antiinflamatorios no esteroidales y glucocorticoides en otros hospitales, pero los efectos fueron leves y las c ondiciones reemergieron. El LS ha durado más de tres meses. Siguiendo el tratamiento de medicina tradicional china (MTC), la diferenciación de síndrome, así como darles a los pacientes una decocción de medicina china por vía oral, los síntomas de la pacien te rápidamente fueron aliviados en el curso de una semana y no recidivaron durante los seis meses de un seguimiento. El caso es el primer reporte clínico de tratamiento de sarcoidosis aguda asociada a LS usando TCM y refleja las significativas ventajas de esta forma de terapia en el tratamiento de emergencia.

Brain volumes and white matter diffusion across the adult lifespan in temporal lobe epilepsy.

OBJECTIVE: Typical aging is associated with gradual cognitive decline and changes in brain structure. The observation that cognitive performance in mesial temporal lobe epilepsy (TLE) patients diverges from controls early in life with subsequent decline running in parallel would suggest an initial insult but does not support accelerated decline secondary to seizures. Whether TLE patients demonstrate similar trajectories of age-related gray (GM) and white matter (WM) changes as compared to healthy controls remains uncertain. METHODS: 3D T1-weighted and diffusion tensor images were acquired at a single site in 170 TLE patients (aged 23-74 years) with MRI signs of unilateral hippocampal sclerosis (HS, 77 right) and 111 healthy controls (aged 26-80 years). Global brain (GM, WM, total brain, and cerebrospinal fluid) and regional volumes (ipsi- and contralateral hippocampi), and fractional anisotropy (FA) of 10 tracts (three portions of corpus callosum, inferior longitudinal, inferior fronto-occipital and uncinate fasciculi, body of fornix, dorsal and parahippocampal-cingulum, and corticospinal tract) were compared between groups as a function of age. RESULTS: There were significant reductions of global brain and hippocampi volumes (greatest ipsilateral to HS), and FA of all 10 tracts in TLE versus controls. For TLE patients, regression lines run in parallel to those from controls for brain volumes and FA (for all tracts except the parahippocampal-cingulum and corticospinal tract) versus age across the adult lifespan. INTERPRETATION: These results imply a developmental hindrance occurring earlier in life (likely in childhood/neurodevelopmental stages) rather than accelerated atrophy/degeneration of most brain structures herein analyzed in patients with TLE.

Repetitive transcranial magnetic stimulation for treatment of limb spasticity following multiple sclerosis: a systematic review and meta-analysis.

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials.

PFAS in fish from AFFF-impacted environments: Analytical method development and field application at a Canadian international civilian airport.

Methods targeting anionic per- and polyfluoroalkyl substances (PFAS) in aquatic biota are well established, but commonly overlook many PFAS classes present in aqueous film-forming foams (AFFFs). Here, we developed an analytical method for the expanded analysis of negative and positive ion mode PFAS in fish tissues. Eight variations of extraction solvents and clean-up protocols were first tested to recover 70 AFFF-derived PFAS from the fish matrix. Anionic, zwitterionic, and cationic PFAS displayed the best responses with methanol-based ultrasonication methods. The response of long-chain PFAS was improved for extracts submitted to graphite filtration alone compared with those involving solid-phase extraction. The validation included an assessment of linearity, absolute recovery, matrix effects, accuracy, intraday/interday precision, and trueness. The method was applied to a set of freshwater fish samples collected in 2020 in the immediate vicinity (creek, n = 15) and downstream (river, n = 15) of an active fire-training area at an international civilian airport in Ontario, Canada. While zwitterionic fluorotelomer betaines were major components of the subsurface AFFF source zone, they were rarely detected in fish, suggesting limited bioaccumulation potential. PFOS largely dominated the PFAS profile, with record-high concentrations in brook sticklebacks (Culaea inconstans) from the creek (16000-110,000 ng/g wet weight whole-body). These levels exceeded the Canadian Federal Environmental Quality Guidelines (FEQG) for PFOS pertaining to the Federal Fish Tissue Guideline (FFTG) for fish protection and Federal Wildlife Diet Guidelines (FWiDG) for the protection of mammalian and avian consumers of aquatic biota. Perfluorohexane sulfonamide and 6:2 fluorotelomer sulfonate were among the precursors detected at the highest levels (maximum of ∼340 ng/g and ∼1100 ng/g, respectively), likely reflecting extensive degradation and/or biotransformation of C6 precursors originally present in AFFF formulations.

Trends in Online Search Activity and the Correlation with Daily New Cases of Monkeypox among 102 Countries or Territories.

Research assessing the trend in online search activity on monkeypox (mpox) and the correlation with the mpox epidemic at the global and national level is scarce. The trend of online search activity and the time-lag correlations between it and daily new mpox cases were estimated by using segmented interrupted time-series analysis and Spearman correlation coefficient (rs), respectively. We found that after the declaration of a Public Health Emergency of International Concern (PHEIC), the proportion of countries or territories with increasing changes in online search activity was lowest in Africa (8.16%, 4/49), and a downward trend in online search activity was highest in North America (8/31, 25.81%). The time-lag effect of global online search activity on daily new cases was significant (rs = 0.24). There were eight countries or territories with significant time-lag effect; the top three countries or territories were Brazil (rs = 0.46), United States (rs = 0.24), and Canada (rs = 0.24). Interest behavior in mpox was insufficient, even after the declaration of PHEIC, especially in Africa and North America. Online search activity could be used as an early indicator of the outbreak of mpox at the global level and in epidemic countries.

Repetitive transcranial magnetic stimulation for treatment of limb spasticity following multiple sclerosis: a systematic review and meta-analysis

Pilot trials have suggested that repetitive transcranial magnetic stimulation (rTMS) may reduce limb spasticity in multiple sclerosis (MS). We carried out the current meta-analysis to synthesize currently available evidence regarding such correlation. Up to November 2022, five international electronic databases (Cochrane CENTRAL, PubMed, Embase, Web of Science, and CINAHL) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched to identify randomized trials comparing active rTMS and sham stimulation in patients with MS-related spasticity. Two reviewers independently selected studies and extracted data on study design, quality, clinical outcomes, and time points measured. The primary outcome was clinical spasticity relief after intervention. Secondary outcomes included spasticity at the follow-up visit 2 weeks later and post-treatment fatigue. Of 831 titles found, we included 8 studies (181 participants) in the quantitative analysis. Pooled analyses showed that rTMS therapy was associated with significant spasticity relief in the early post-intervention period [standardized mean differences (SMD): -0.67; 95%CI: -1.12 to -0.21], but there was insufficient evidence for rTMS in reducing spasticity at the follow-up visit 2 weeks later (SMD: -0.17; 95%CI: -0.52 to 0.17) and fatigue (SMD: -0.26; 95%CI: -0.84 to 0.31). This evidence supports the recommendations to treat MS-related spasticity with rTMS, but underlines the need for further large randomized trials.

Effects of functional training on the performance of sedentary college students / Efeitos do treinamento funcional sobre o desempenho de universitários sedentários / Efectos del entrenamiento funcional en el rendimiento de universitarios sedentarios

ABSTRACT Introduction: One focus of current research by frontline physical education teachers has always been the elective teaching of college students who do not play sports. Lack of training time and poor student training make many professional badminton teaching methods impossible for elective courses. Objective: Study the impact of functional training on the badminton performance of college students. Methods: Forty-four sedentary college students were randomly selected and equally divided into the experimental and control group. The functional training strategy was used in the experimental group, while the control group used the traditional badminton training method. The experimental and control groups were trained twice weekly for 60 minutes and 12 weeks. The data obtained were compared, analyzed, and discussed statistically. Results: In terms of the FMS test, the total score of the experimental group was optimized by 5.61, and the total score of the control group was optimized by 3.20. Regarding badminton performance, the experimental group showed an increase of 23.12 points, while the control group increased 16.75 points (P<0.01), indicating a very significant difference in the results. Conclusion: This work evidenced the importance of promoting functional training, which is superior to the current sports teaching methods. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Um dos focos das pesquisas atuais dos professores de educação física na linha de frente tem sido sempre o ensino eletivo de estudantes universitários que não praticam esportes. A falta de tempo de treinamento e a deficiente formação dos estudantes tornam muitos métodos profissionais de ensino de badminton impossíveis de serem realizados em cursos optativos. Objetivo: Estudar o impacto do treinamento funcional sobre o desempenho de badminton dos estudantes universitários. Métodos: Foram selecionados aleatoriamente 44 universitários sedentários, divididos igualmente em grupo experimental e controle. No grupo experimental foi utilizada a estratégia de treinamento funcional, enquanto o grupo de controle usou o método tradicional de treinamento de badminton. Tanto o grupo experimental quanto o grupo controle treinaram duas vezes por semana, por 60 minutos e durante 12 semanas. Os dados obtidos comparados, analisados e discutidos estatisticamente. Resultados: Em termos de teste FMS, a pontuação total do grupo experimental foi otimizada em 5,61, e a pontuação total do grupo de controle foi otimizada em 3,20. Com relação ao desempenho do badminton, o grupo experimental apresentou um aumento de 23,12 pontos, enquanto que o grupo controle aumentou 16.75 pontos (P<0.01), indicando que houve uma diferença muito significativa dos resultados. Conclusão: Este trabalho evidenciou a importância da promoção do treinamento funcional, comparativamente superior aos métodos de ensino esportivo praticados atualmente. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Uno de los focos de la investigación actual de los profesores de educación física de primera línea ha sido siempre la enseñanza optativa de los estudiantes universitarios que no practican deportes. La falta de tiempo de entrenamiento y la escasa formación de los alumnos hacen que muchos métodos profesionales de enseñanza del bádminton resulten imposibles para los cursos optativos. Objetivo: Estudiar el impacto del entrenamiento funcional en el rendimiento en bádminton de estudiantes universitarios. Métodos: Se seleccionaron aleatoriamente 44 estudiantes universitarios sedentarios y se dividieron equitativamente en grupo experimental y grupo de control. En el grupo experimental se utilizó la estrategia de entrenamiento funcional, mientras que el grupo de control utilizó el método tradicional de entrenamiento de bádminton. Tanto el grupo experimental como el de control entrenaron dos veces por semana, durante 60 minutos y durante 12 semanas. Los datos obtenidos se comparan, analizan y discuten estadísticamente. Resultados: En términos de la prueba FMS, la puntuación total del grupo experimental se optimizó en 5,61, y la puntuación total del grupo de control se optimizó en 3,20. En cuanto al rendimiento en bádminton, el grupo experimental mostró un aumento de 23,12 puntos, mientras que el grupo de control aumentó 16,75 puntos (P<0,01), lo que indica que hubo una diferencia muy significativa en los resultados. Conclusión: Este trabajo evidenció la importancia de promover el entrenamiento funcional, comparativamente superior a los métodos de enseñanza deportiva practicados actualmente. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Strength and quality training of basketball players / Força e treinamento de qualidade dos jogadores de basquetebol / Fuerza y entrenamiento de calidad de los jugadores de baloncesto

ABSTRACT Introduction: Quality exercise training of young people is a fundamental basic requirement for developing physical fitness in college basketball teaching. Objective: Enhance exercise training in young basketball players. Methods: A random selection of 50 student volunteers was made for this research. The strength and quality of basketball players of different ages were analyzed. The experimental group was subjected to specific strength training, while the control group was subjected to routine physical exercises. The experiment period was 12 weeks, and the specific technical indicators of the athletes were collected before and after the end of the experiment. The collected data were statistically treated and discussed in light of the scientific literature. Results: No significant difference was found between the two groups in the initial test score (P>0.05). The experimental group's performance in exercise was better than the control group after 12 weeks (P<0.01). The experimental group demonstrated better performance than the control group in the standing jump, 15-meter reentry, and forward jump, corroborating the significantly different data between the two groups (P<0.01). Conclusion: This study aimed to study the unique role of strength training in the physical training of young basketball players. Special strength training positively affects upper limb muscle training in young basketball players. The lower extremities of basketball players showed expressive functional gains with special strength training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O exercício físico de qualidade dos jovens é requisito básico fundamental para o desenvolvimento da aptidão física no ensino do basquetebol universitário. Objetivo: Fortalecer o treinamento do exercício físico em jovens jogadores de basquetebol. Métodos: Efetuou-se a seleção aleatória de 50 estudantes voluntários para a pesquisa. Foi analisada a força e a qualidade dos jogadores de basquetebol em diferentes idades. O grupo experimental foi submetido a um treinamento de força específica, enquanto o grupo de controle foi submetido a exercícios físicos de rotina. O período do experimento foi de 12 semanas e os indicadores técnicos específicos dos atletas foram coletados antes e após a finalização do experimento. Os dados coletados foram tratados estatisticamente e discutidos à luz da literatura científica. Resultados: Não foi encontrada diferença significativa entre os dois grupos na pontuação inicial do teste (P>0,05). O desempenho do grupo experimental no exercício foi melhor que o do grupo de controle após as 12 semanas (P<0,01). O grupo experimental demonstrou um desempenho melhor que o do grupo controle no salto em pé, reentrada de 15 metros, e salto de frente, corroborando com os dados significativamente distintos entre os dois grupos (P<0,01). Conclusão: Este estudo teve como objetivo estudar o papel único do treinamento de força no treinamento físico dos jovens jogadores de basquetebol. O treinamento especial de força afeta positivamente o treinamento muscular dos membros superiores nos jovens jogadores de basquetebol. As extremidades inferiores dos jogadores de basquetebol evidenciaram ganhos funcionais expressivos com o treinamento especial de força. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El ejercicio físico de calidad de los jóvenes es un requisito básico fundamental para el desarrollo de la aptitud física en la enseñanza del baloncesto universitario. Objetivo: Reforzar el entrenamiento del ejercicio físico en jóvenes jugadores de baloncesto. Métodos: Se realizó una selección aleatoria de 50 estudiantes voluntarios para la investigación. Se analizó la fuerza y la calidad de los jugadores de baloncesto a diferentes edades. El grupo experimental fue sometido a un entrenamiento de fuerza específico, mientras que el grupo de control fue sometido a ejercicios físicos rutinarios. El periodo del experimento fue de 12 semanas y se recogieron los indicadores técnicos específicos de los atletas antes y después de finalizar el experimento. Los datos recogidos fueron tratados estadísticamente y discutidos a la luz de la literatura científica. Resultados: No se encontraron diferencias significativas entre los dos grupos en la puntuación de la prueba inicial (P>0,05). El rendimiento del grupo experimental en el ejercicio fue mejor que el del grupo de control después de 12 semanas (P<0,01). El grupo experimental mostró un mejor rendimiento que el grupo de control en el salto de pie, el reingreso de 15 metros y el salto frontal, corroborando los datos significativamente diferentes entre los dos grupos (P<0,01). Conclusión: Este estudio tenía como objetivo estudiar el papel único del entrenamiento de la fuerza en la preparación física de los jóvenes jugadores de baloncesto. El entrenamiento de fuerza especial afecta positivamente al entrenamiento muscular de las extremidades superiores en jóvenes jugadores de baloncesto. Las extremidades inferiores de los jugadores de baloncesto mostraron ganancias funcionales expresivas con el entrenamiento de fuerza especial. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Structural insights into the cyclization of unusual brasilane-type sesquiterpenes.

The biosynthesis of brasilane-type sesquiterpenoids (BTSs) attracts much attention owing to their unique skeleton of 5/6 bicyclic structure that contains five Me groups. Here, the crystal structures of a BTS cyclase TaTC6 from Trichoderma atroviride FKI-3849 and its complexes with farnesyl pyrophosphate (FPP) and analogue were reported. These structural information reveal that TaTC6 exploits a hydrophobic pocket to constrain the hydrocarbon region of FPP in a "U-shape" to facilitate the initial C1-C11 bond formation after pyrophosphate ionization. Following, four carbocations of reaction intermediates were molecularly docked into the hydrophobic pocket to reveal critical residues involved in the cyclization cascade. Finally, an S239-stabilized water molecule that is 3.9 Å away from the C8 of the last allyl cation may conduct hydration to quench the reaction cascade. Mutating S239 to alanine led to ca. 40% reduction in activity compared with the wild-type enzyme. The conservation of the residues that constitute the hydrophobic pocket is also discussed. Overall, this study will give an insight into the mechanism of how the active site of STCs constrain the conformation of the flexible FPP and series allylic carbocations for the complicated-ring formation and unusual carbon rearrangement in the biosynthesis of BTSs.

Identification of immunophenotypes in esophageal squamous cell carcinoma based on immune gene sets.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high heterogeneity. Research on molecular mechanisms involved in the process of tumor origination and progression is extremely limited to investigating mechanisms of molecular typing for ESCC. METHODS: After comprehensively analyzing the gene expression profiles in The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified four immunotypes of ESCC (referred to as C1-C4) based on the gene sets of 28 immune cell subpopulations. The discrepancies in prognostic value, clinical features, drug sensitivity, and tumor components between the immunotypes were individually analyzed. RESULTS: The ranking of immune infiltration is C1 > C4 > C3 > C2. These subtypes are characterized by high and low expression of immune checkpoint proteins, enrichment and insufficiency of immune-related pathways, and differential distribution of immune cell subgroups. Poorer survival was observed in the C1 subtype, which we hypothesized could be caused by an immunosuppressive cell population. Fortunately, C1's susceptibility to anti-PD-1 therapy offers hope for patients with poor prognosis in advanced stages. On the other hand, C4 is sensitive to docetaxel, which may offer novel treatment strategies for ESCC in the future. It is worth noting that immunophenotyping is tightly bound to the abundance of stromal components and stem cells, which could explain the tumor immune escape to some extent. Ultimately, determination of hub genes based on the C1 subtypes provides a reference for the discovery of immunotarget drugs against ESCC. CONCLUSION: The identification of immunophenotypes in our study provides new therapeutic strategies for patients with ESCC.

Prevalence of toothache in Chinese adults aged 65 years and above.

OBJECTIVES: To investigate the prevalence of toothache and its risk indicators in the older Chinese population. METHODS: National cross-sectional survey data on 25 048 Chinese people ≥65 years in 2011, 2014 and 2018 survey year were analysed and then pooled. Chi-square test was used to examine the differences in prevalence among specific subgroups. Multivariate modified Poisson regression analyses with robust error variances were used to detect related factors and prevalence ratios (PR) were calculated. RESULTS: The prevalence of toothache was 16.3% (95% CI: 15.5%-17.1%), 12.8% (95% CI: 12.0%-13.7%) and 16.0% (95% CI: 15.3%-16.7%) in years 2011, 2014 and 2018. In the pooled multivariate Poisson regression model, factors associated with toothache were female (PR: 1.27, 95% CI: 1.18-1.37), younger age (PR: 1.84, 95% CI: 1.63-2.09), currently married and living with spouse (PR: 1.08, 95% CI: 1.01-1.15), current living in urban area (PR:1.12, 95% CI: 1.06-1.20), enough financial support (PR: 0.69, 95% CI: 0.65-0.74), having chronic disease (PR: 1.46, 95% CI: 1.35, 1.57), higher sugar intake (PR: 1.10, 95% CI: 1.03-1.17), salty flavour (PR:1.15, 95% CI: 1.07-1.23), smoking (PR: 1.14, 95% CI:1.06-1.23) or drinking (PR: 1.17, 95% CI: 1.09-1.25), with denture (PR: 1.15, 95% CI: 1.08-1.22) and higher toothbrushing frequency (PR: 1.25-1.50). CONCLUSIONS: More than one in ten older Chinese population had toothache, and it was related to age, gender, socioeconomic status, behaviour and oral health status. Lifestyle interventions should be taken to avoid the occurrence of the toothache.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway.

PURPOSE: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. METHODS: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. RESULTS: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1ß, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. CONCLUSION: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-B/NLRP3 signaling pathway

Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1, IL-18, IL-6 and TNF-) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.(AU)

HNSCC subverts PBMCs to secrete soluble products that promote tumor cell proliferation.

The immune system detects shifts from homeostasis and eliminates altered cells. However, neoplastic cells can modulate the host response to escape immunosurveillance thereby allowing tumor progression. Head and neck squamous cell carcinoma (HNSCC) is one of the most immunosuppressive cancers but its role in co-opting the immune system to actively promote tumor growth has not been investigated. In this study, we investigated the influence of soluble factors secreted by HNSCC and non-neoplastic epithelial cells on proliferation, apoptosis, activation, cytokine gene expression and phenotypic polarization of immune cells of healthy donors. Then, we determined if the immunomodulation caused by HNSCC-derived soluble products leads to immunosubversion by assessing proliferation, migration and survival of tumor cells exposed to soluble products secreted by modulated immune cells or co-cultured with immune cells. Soluble products from HNSCC inhibited proliferation and cytokine expression in PBMCs, activation of T cells, and polarization of CD4+ towards the Th17 phenotype. These changes co-opted the immune cells to favor cell proliferation, survival and migration of HNSCC. This immunosubversion was observed both indirectly with secreted products and with direct cell-to-cell contact. We conclude that HNSCC-derived secreted products create an immunosuppressive environment that facilitates evasion of tumor cells and subverts the immune cells into a pro-tumoral phenotype.

Cholesterol and Lipoprotein Metabolism and Atherosclerosis: Recent Advances In reverse Cholesterol Transport.

Atherosclerosis is characterized by lipid accumulation, inflammatory response, cell death and fibrosis in the arterial wall, and is major pathological basis for ischemic coronary heart disease (CHD), which is the leading cause of morbidity and mortality in the USA and Europe. Intervention studies with statins have shown to reduce LDL cholesterol levels and subsequently the risk of developing CHD. However, not all the aggressive statin therapy could decrease the risk of developing CHD. Many clinical and epidemiological studies have clearly demonstrated that the HDL cholesterol is inversely associated with risk of CHD and is a critical and independent component of predicting its risk. Elucidations of HDL metabolism give rise to therapeutic targets with potential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. The concept of reverse cholesterol transport is based on the hypothesis that HDL displays an cardioprotective function, which is a process involved in the removal of excess cholesterol that is accumulated in the peripheral tissues (e.g., macrophages in the aortae) by HDL, transporting it to the liver for excretion into the feces via the bile. In this review, we summarize the latest advances in the role of the lymphatic route in reverse cholesterol transport, as well as the biliary and the non-biliary pathways for removal of cholesterol from the body. These studies will greatly increase the likelihood of discovering new lipid-lowering drugs, which are more effective in the prevention and therapeutic intervention of CHD that is the major cause of human death and disability worldwide.

Risk Factors for No-Reflow Phenomenon after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.

BACKGROUND: To explore risk factors for no-reflow phenomenon after percutaneous coronary intervention in patients with acute coronary syndrome. METHODS: A total of 733 acute myocardial infarction patients with persistent ischemic chest pain within 12 or 12-24 hours after onset received emergency percutaneous coronary intervention. Patients were divided into a normal reflow group and a no-reflow group, according to TIMI grading and myocardial blush grading after percutaneous coronary intervention. Related risk factors were analyzed. RESULTS: The incidence of no-reflow phenomenon after percutaneous coronary intervention was 16.1%. Univariate analysis showed that, compared with the normal reflow group, the no-reflow group was older, reperfusion time was significantly longer, preoperative systolic pressure was lower, troponin peak was higher, and creatine kinase enzyme peak was higher (p < 0.05). The proportions of preoperative cardiac function Killip grade ≥ 2 and number of patients using preoperative intra-aortic balloon pump were significantly different (p < 0.05). Multivariate logistic regression analysis showed that age > 65 years (OR: 1.471; 95% CI: 1.462-1.492; p = 0.007), reperfusion time > 6 hours (OR: 1.274; 95% CI: 1.164-1.405; p = 0.001), low systolic pressure at admission (< 100 mmHg) (OR: 1.918; 95% CI: 1.017-3.897; p = 0.004), intra-aortic balloon pump use before percutaneous coronary intervention (OR: 1.949; 95% CI: 1.168-3.253; p = 0.011), low TIMI grade (≤ 1) before percutaneous coronary intervention (OR: 1.100; 95% CI: 1.086-1.257; p < 0.01), high thrombus load (OR: 1.274; 95% CI: 1.423-2.761; p = 0.030), and long target lesion (OR: 1.948; 95% CI: 1.908-1.990; p = 0.019) were independent risk factors. CONCLUSIONS: No-reflow phenomenon after percutaneous coronary intervention in patients with acute coronary syndrome was affected by complicated pathological factors.

Compound heterozygous MYO7A mutations segregating Usher syndrome type 2 in a Han family.

OBJECTIVE: Identification of rare deafness genes for inherited congenital sensorineural hearing impairment remains difficult, because a large variety of genes are implicated. In this study we applied targeted capture and next-generation sequencing to uncover the underlying gene in a three-generation Han family segregating recessive inherited hearing loss and retinitis pigmentosa. METHODS: After excluding mutations in common deafness genes GJB2, SLC26A4 and the mitochondrial gene, genomic DNA of the proband of a Han family was subjected to targeted next-generation sequencing. The candidate mutations were confirmed by Sanger sequencing and subsequently analyzed with in silico tools. RESULTS: An unreported splice site mutation c.3924+1G > C compound with c.6028G > A in the MYO7A gene were detected to cosegregate with the phenotype in this pedigree. Both mutations, located in the evolutionarily conserved FERM domain in myosin VIIA, were predicted to be pathogenic. In this family, profound sensorineural hearing impairment and retinitis pigmentosa without vestibular disorder, constituted the typical Usher syndrome type 2. CONCLUSION: Identification of novel mutation in compound heterozygosity in MYO7A gene revealed the genetic origin of Usher syndrome type 2 in this Han family.

ADRB2 polymorphisms predict the risk of myocardial infarction and coronary artery disease.

Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.

White matter abnormalities associate with type and localization of focal epileptogenic lesions.

OBJECTIVE: To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)-resistant localization-related epilepsies. METHODS: We used diffusion tensor imaging (DTI) fiber-tractography and voxel-based morphometry (VBM) to investigate differences of WM micro- and macrostructural integrity in patients with different drug-resistant localization-related epilepsies: 17 with temporal lobe epilepsy with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 17 with TLE and normal MRI (TLE-NL), 14 with frontal lobe epilepsy and subtle MRI signs of focal cortical dysplasia (FLE-FCD), and 112 healthy controls. We performed fiber-tractography using a semiautomatic deterministic method to yield average fractional anisotropy (FA), axial (AD), and radial (RD) diffusivity ipsilateral and contralateral to the epileptogenic zone of the following tracts based on their functional and anatomic relevance: body of fornix (BoF), body of cingulum (BoC), inferior frontal occipital (IFO), and uncinate fasciculi (UF). In addition, we performed VBM of the WM maps to assess macrostructural integrity differences among groups. RESULTS: TLE-HS had ipsilateral and contralateral decreased FA and increased RD for all tracts. VBM showed WM alterations mainly in the ipsilateral parahippocampal region and contralateral superior temporal gyrus. FLE-FCD showed bilateral FA decreases only in the BoC and ipsilateral RD increases also in the BoC. VBM showed WM reduction mainly in the ipsilateral precuneus and posterior and anterior cingulum. No significant WM alterations were found in the TLE-NL in DTI or VBM analysis. SIGNIFICANCE: WM abnormalities differ in distinct AED-resistant localization-related epilepsies. The diverse distribution of the WM damage in these patients suggests that the localization of the epileptic networks may play a role in the WM burden. However, the distinct degree of this damage, more accentuated in TLE-HS, also suggests that the underlying cause of the epilepsy is probably an additional factor to explain this WM damage.