The Role of Marein During Endothelial-Mesenchymal Transition in Diabetic Kidney Disease / Rol de la Mareína Durante la Transición Endotelial-Mesenquimatosa en la Enfermedad Renal Diabética

SUMMARY: Marein is a flavonoid compound that reduces blood glucose and lipids and has a protective effect in diabetes. However, the effect and mechanism(s) of marein on renal endothelial-mesenchymal transition in diabetic kidney disease (DKD) have not been elucidated. In this study, single-cell sequencing data on DKD were analyzed using a bioinformation method, and the data underwent reduced dimension clustering. It was found that endothelial cells could be divided into five subclusters. The developmental sequence of the subclusters was 0, 1, 4, 2, and 3, of which subcluster 3 had the most interstitial phenotype.The expression of mesenchymal marker protein:Vimentin(VIM), Fibronectin(FN1), and fibroblast growth factor receptor 1 (FGFR1) increased with the conversion of subclusters. In db/db mice aged 13-14 weeks, which develop DKD complications after 8-12 weeks of age, marein reduced blood levels of glucose, creatinine, and urea nitrogen, improved structural damage in kidney tissue, and reduced collagen deposition and the expression of FN1 and VIM. Marein also up-regulated autophagy marker:Light chain 3II/I(LC3II/I) and decreased FGFR1 expression in renal tissue. In an endothelial-mesenchymal transition model, a high glucose level induced a phenotypic change in human umbilical vein endothelial cells. Marein decreased endothelial cell migration, improved endothelial cell morphology, and decreased the expression of VIM and FN1. The use of the FGFR1 inhibitor, AZD4547, and autophagy inhibitor, 3-Methyladenine(3-MA), further demonstrated the inhibitory effect of marein on high glucose-induced endothelial-mesenchymal transition by reducing FGFR1 expression and up-regulating the autophagy marker protein, LC3II/I. In conclusion, this study suggests that marein has a protective effect on renal endothelial- mesenchymal transition in DKD, which may be mediated by inducing autophagy and down-regulating FGFR1 expression.

La mareína es un compuesto flavonoide que reduce la glucosa y los lípidos en sangre y tiene un efecto protector en la diabetes. Sin embargo, no se han dilucidado el efecto y los mecanismos de la mareína sobre la transición endotelial- mesenquimatosa renal en la enfermedad renal diabética (ERD). En este estudio, los datos de secuenciación unicelular sobre DKD se analizaron utilizando un método de bioinformación y los datos se sometieron a una agrupación de dimensiones reducidas. Se descubrió que las células endoteliales podían dividirse en cinco subgrupos. La secuencia de desarrollo de los subgrupos fue 0, 1, 4, 2 y 3, de los cuales el subgrupo 3 tenía el fenotipo más intersticial. La expresión de la proteína marcadora mesenquimatosa: vimentina (VIM), fibronectina (FN1) y receptor del factor de crecimiento de fibroblastos. 1 (FGFR1) aumentó con la conversión de subgrupos. En ratones db/db de 13 a 14 semanas de edad, que desarrollan complicaciones de DKD después de las 8 a 12 semanas de edad, la mareína redujo los niveles sanguíneos de glucosa, creatinina y nitrógeno ureico, mejoró el daño estructural en el tejido renal y redujo la deposición y expresión de colágeno de FN1 y VIM. Marein también aumentó el marcador de autofagia: Cadena ligera 3II/I (LC3II/I) y disminuyó la expresión de FGFR1 en el tejido renal. En un modelo de transición endotelial-mesenquimal, un nivel alto de glucosa indujo un cambio fenotípico en las células endoteliales de la vena umbilical humana. Marein disminuyó la migración de células endoteliales, mejoró la morfología de las células endoteliales y disminuyó la expresión de VIM y FN1. El uso del inhibidor de FGFR1, AZD4547, y del inhibidor de la autofagia, 3-metiladenina (3-MA), demostró aún más el efecto inhibidor de la mareína en la transición endotelial-mesenquimal inducida por niveles altos de glucosa al reducir la expresión de FGFR1 y regular positivamente la proteína marcadora de autofagia. , LC3II/I. En conclusión, este estudio sugiere que la mareína tiene un efecto protector sobre la transición endotelial-mesenquimatosa renal en la ERC, que puede estar mediada por la inducción de autofagia y la regulación negativa de la expresión de FGFR1.

Single-Slice Hounsfield Unit (HU) Value of the Chinese Proximal Humerus on Routine Chest CT: A Study on Opportunistically Screening for Low Bone Density / Valor de Unidad Hounsfield (HU) de Corte Único del Húmero Proximal Chino en una Tomografía Computarizada de Tórax de Rutina: Un Estudio sobre la Detección Oportunista de Baja Densidad Ósea

SUMMARY: A Study on Relationship between Single-Slice Hounsfield Unit(HU) value of the Chinese proximal humerus and Bone Mineral Density(BMD) Using Routine Chest CT and Dual-energy X-ray Absorptiometry(DEXA) was performed. Data were collected from 240 individuals who underwent DEXA and routine chest CT scans (including full images of the proximal humerus) on the same day at 967 Hospitals between January 2019 and December 2021. The method of measuring single-slice HU values of the proximal humerus on routine chest CT scans exhibited high reliability and repeatability (intraclass correlation coefficient > 0.961, P < 0.001). A strong positive correlation was observed between single-slice HU values of the proximal humerus and DEXA results, with the 20-mm HU value demonstrating the highest correlation. Across different BMI groups, the Area Under Curve (AUC) for the 20-mm HU value was consistently the largest (AUC=0.701- 0.813, P< 0.05). Therefore, the 20-mm HU value can be considered a reliable reference for the opportunistic screening of low BMD, with reference values of -4HU for underweight individuals, -13HU for normal weight individuals, -7HU for overweight individuals, and -16HU for obese individuals. Values below these thresholds indicate a risk of low BMD. This study enriches the Chinese BMD data and offers a swift and effective approach for opportunistically screening low BMD.

Se realizó un estudio sobre la relación entre el valor de la Unidad Hounsfield (HU) de corte único del húmero proximal chino y la densidad mineral ósea (DMO) mediante TC de tórax de rutina y absorciometría de rayos X de energía dual (DEXA). Se recopilaron datos de 240 personas que se sometieron a DEXA y tomografías computarizadas de rutina de tórax (incluidas imágenes completas del húmero proximal) el mismo día en 967 hospitales entre enero de 2019 y diciembre de 2021. El método para medir los valores de HU de un solo corte del húmero proximal en las tomografías computarizadas de tórax mostraron alta confiabilidad y repetibilidad (coeficiente de correlación intraclase > 0,961, P < 0,001). Se observó una fuerte correlación positiva entre los valores de HU de un solo corte del húmero proximal y los resultados de DEXA, demostrando el valor de HU de 20 mm la correlación más alta. En diferentes grupos de IMC, el área bajo la curva (AUC) para el valor HU de 20 mm fue consistentemente el más grande (AUC = 0,701-0,813, P <0,05). Por lo tanto, el valor de HU de 20 mm puede considerarse una referencia fiable para el cribado oportunista de DMO baja, con valores de referencia de -4 HU para personas con bajo peso, -13 HU para personas con peso normal, -7 HU para personas con sobrepeso y -16 HU para personas obesas. Los valores por debajo de estos umbrales indican un riesgo de DMO baja. Este estudio es un aporte para los datos chinos sobre la DMO y ofrece un enfoque rápido y eficaz para detectar de forma oportunista la DMO baja.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Mental health difficulties and related factors in Chinese children and adolescents during the COVID-19 pandemic: a cross-sectional study

Abstract Objective: To examine the mental health status and related factors in children and adolescents, and to assess age groups and sexes differences in factors influencing mental health. Methods: This cross-sectional study was performed on Chinese children aged 6-18 years from November 2021 to January 2022. Mental health difficulties were accessed by the Strengths and Difficulties Questionnaire. Multivariate logistic regression was used to analyze factors associated with mental health status. Multiple linear regression was used to evaluate factors associated with the scores of the Strengths and Difficulties Questionnaire. Results: The prevalence of mental health difficulties was 12.98% (n =1348). Age (OR, 0.909, [95%CI, 0.830-0.996]), sex (OR, 1.424, [95%CI, 1.033-1.963]) and screen time on weekdays ("≥2" h/d vs "< 1" h/d: OR, 2.001, [95%CI, 1.300-3.080]) were related factors for mental health difficulties. For children (year ≤ 12), the strongest related factor for mental health difficulties was screen time on weekdays ("≥ 2" h/d vs "< 1" h/d: OR, 1.821 [95%CI, 1.203-2.755]). The risk of mental health difficulties in females with ≥ 2 h/d screen time on weekends was 3.420 times higher than those with < 1 h/d (OR, 3.420, [95%CI, 1.923-6.081]). Conclusion: The prevalence of mental health difficulties among children and adolescents was relatively high. The lower age, female sex and excessive screen time were associated with a higher risk of mental health difficulties. The factors influencing mental health varied by different age groups and sexes. Thus, specific measures for different age groups and sexes should be adopted to mitigate the impact.

Clinical characteristics of neonatal and infant osteomyelitis and septic arthritis: a multicenter retrospective study

Abstract Objective: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. Methods: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. Results: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). Conclusion: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Abstract Objective: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. Method: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. Results: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4% (p = 0.006). Conclusion: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Ethical assessment of privacy breaches in epidemiological investigations and information disclosure in the internet age: safeguarding identity information for infectious patients

While the Internet has brought convenience and speed to human life, it has also led to frequent privacy violations. In the context of epidemiological investigations and information disclosure regarding confirmed Covid-19 patients, many individuals have utilized the Internet as a means to disseminate information and engage in cyber manhunts, resulting in breaches of privacy for those involved. This phenomenon is particularly prevalent within the realm of the Internet, where the boundaries of privacy invasion become blurred. Various types of privacy infringements, both active and passive negligence, are evident on social networking platforms. The juxtaposition of the virtual world of the Internet with real-life scenarios presents novel challenges in the realm of privacy violations. The Internet era, coupled with the widespread use and integration of big data, has diminished the absolute right to privacy on the Internet. This paper examines the challenge of safeguarding the identity information of infectious patients through the lens of two theoretical frameworks -Kantianism and Utilitarianism- in an effort to address this ethical dilemma.

Aunque Internet ha aportado comodidad y rapidez a la vida humana, también ha dado lugar a frecuentes violaciones de la intimidad. En el contexto de las investigaciones epidemiológicas y la divulgación de información relativa a pacientes confirmados de covid-19, muchas personas han utilizado Internet como medio para difundir información y participar en cibercacerías, lo que ha dado lugar a violaciones en la intimidad de los implicados. Este fenómeno prevalece en el ámbito de Internet, donde los límites de la invasión de la intimidad se vuelven vagos. En las redes sociales, se manifiestan diversos tipos de violaciones de la intimidad, tanto por negligencia activa como pasiva. La yuxtaposición entre el mundo virtual de Internet con escenarios de la vida real plantea nuevos retos en el ámbito de las violaciones de la intimidad. La era de Internet, junto con el uso generalizado y la integración del bigdata, han mermado el derecho absoluto a la privacidad. Este artículo examina el reto de salvaguardar la información sobre la identidad de los pacientes infecciosos a través de la lente de dos marcos teóricos -el kantianismo y el utilitarismo- en un esfuerzo por abordar este dilema ético.

Enquanto a Internet trouxe conveniência e velocidade à vida humana, ela também levou a frequentes violações da privacidade. No contexto de investigações epidemiológicas e divulgação de informações em relação a pacientes confirmados de Covid-19, muitos indivíduos utilizaram a Internet como um meio para disseminar informação e participar de uma caçada cibernética, resultando em violações da privacidade para aqueles envolvidos. Esse fenômeno é particularmente prevalente no âmbito da Internet, onde os limites de invasão da privacidade se tornaram borrados. Vários tipos de infrações da privacidade, tanto negligências ativa como passiva, são evidentes em plataformas de redes sociais. A justaposição do mundo virtual da Internet com cenários da vida real apresenta novos desafios no âmbito das violações da privacidade. A era da Internet, juntamente com o amplo uso e integração de megadados (big data), diminuiu o direito absoluto à privacidade na Internet. Esse artigo examina o desafio de proteger a informação de identidade de pacientes infectantes através das lentes de dois enquadres teóricos -Kantianismo e Utilitarismo- em um esforço para abordar esse dilema ético.

Development and validation of a diagnostic prediction model for severe periventricular-intraventricular hemorrhage in newborns: insights from a retrospective analysis utilizing the MIMIC-III database

Abstract Objective: Periventricular-intraventricular hemorrhage is the most common type of intracranial bleeding in newborns, especially in the first 3 days after birth. Severe periventricular-intraventricular hemorrhage is considered a progression from mild periventricular-intraventricular hemorrhage and is often closely associated with severe neurological sequelae. However, no specific indicators are available to predict the progression from mild to severe periventricular-intraventricular in early admission. This study aims to establish an early diagnostic prediction model for severe PIVH. Method: This study was a retrospective cohort study with data collected from the MIMIC-III (v1.4) database. Laboratory and clinical data collected within the first 24 h of NICU admission have been used as variables for both univariate and multivariate logistic regression analyses to construct a nomogram-based early prediction model for severe periventricular-intraventricular hemorrhage and subsequently validated. Results: A predictive model was established and represented by a nomogram, it comprised three variables: output, lowest platelet count and use of vasoactive drugs within 24 h of NICU admission. The model's predictive performance showed by the calculated area under the curve was 0.792, indicating good discriminatory power. The calibration plot demonstrated good calibration between observed and predicted outcomes, and the Hosmer-Lemeshow test showed high consistency (p = 0.990). Internal validation showed the calculated area under a curve of 0.788. Conclusions: This severe PIVH predictive model, established by three easily obtainable indicators within the NICU, demonstrated good predictive ability. It offered a more user-friendly and convenient option for neonatologists.

A prediction model for coronary artery abnormalities in children with Kawasaki disease older than 5 years

Abstract Objective: Reliably prediction models for coronary artery abnormalities (CAA) in children aged > 5 years with Kawasaki disease (KD) are still lacking. This study aimed to develop a nomogram model for predicting CAA at 4 to 8 weeks of illness in children with KD older than 5 years. Methods: A total of 644 eligible children were randomly assigned to a training cohort (n = 450) and a validation cohort (n = 194). The least absolute shrinkage and selection operator (LASSO) analysis was used for optimal predictors selection, and multivariate logistic regression was used to develop a nomogram model based on the selected predictors. Area under the receiver operating characteristic curve (AUC), calibration curves, Hosmer-Lemeshow test, Brier score, and decision curve analysis (DCA) were used to assess model performance. Results: Neutrophil to lymphocyte ratio, intravenous immunoglobulin resistance, and maximum baseline z-score ≥ 2.5 were identified by LASSO as significant predictors. The model incorporating these variables showed good discrimination and calibration capacities in both training and validation cohorts. The AUC of the training cohort and validation cohort were 0.854 and 0.850, respectively. The DCA confirmed the clinical usefulness of the nomogram model. Conclusions: A novel nomogram model was established to accurately assess the risk of CAA at 4-8 weeks of onset among KD children older than 5 years, which may aid clinical decisionmaking.

Levosimendana e Fibrilação Atrial: Uma Metanálise de Ensaios Clínicos Randomizados / Levosimendan and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

Resumo Fundamento A fibrilação atrial (FA) é uma complicação prevalente associada à levosimendana; no entanto, permanece incerto se existem disparidades nos efeitos da levosimendana na FA não pós-operatória e pós-operatória. Objetivos Este estudo teve como objetivo avaliar o efeito da levosimendana na FA não pós-operatória e pós-operatória conduzindo uma metanálise de ensaios clínicos randomizados (ECR). Métodos PubMed, Embase, Biblioteca Cochrane e outras bases de dados foram pesquisadas. Pares de revisores identificaram ECRs que compararam levosimendana e placebo ou outras terapias, e os resultados relataram dados de eventos de FA. Foram utilizados modelos de efeitos aleatórios (com nível de significância de 5%). Resultados Foram incluídos 29 ensaios elegíveis compreendendo 6.550 participantes, onze dos quais avaliaram a incidência de FA não pós-operatória e 18 incluíram FA pós-operatória. A análise revelou que a levosimendana elevou significativamente o risco de FA no grupo não pós-operatório (OR, 1,62; IC 95%: 1,19-2,20; p=0,002) e reduziu a incidência de FA no grupo pós-operatório (OR, 0,65; IC 95%: 0,44-0,96; p=0,03). A ocorrência de FA diminuiu mais significativamente em pacientes que usaram levosimendana após cirurgia cardíaca (OR, 0,53; IC 95%: 0,32-0,88; p=0,02) do que em pacientes que usaram levosimendana antes da cirurgia cardíaca (OR, 0,67; IC 95%: 0,42-1,06; p=0,09). O risco de FA foi significativamente elevado pela grande dose em bolus de levosimendana (dose em bolus ≥12 μg/kg) (OR, 1,44; IC 95%: 1,10-1,88; p=0,004) e diminuído pela pequena dose em bolus de levosimendana (dose em bolus <12 μg/kg) (OR, 0,64; IC 95%: 0,34-1,20; p=0,16). Conclusão A levosimendana foi associada a um aumento da incidência de FA não pós-operatória. O emprego da levosimendana foi eficaz na prevenção da FA pós-operatória.

Abstract Background Atrial fibrillation (AF) is a prevalent complication associated with levosimendan; however, it remains uncertain whether there are any disparities in the effects of levosimendan on non-postoperative and postoperative AF. Objectives This study aimed to evaluate the levosimendan effect on non-postoperative and postoperative AF by conducting a meta-analysis of randomized control trials (RCTs). Methods PubMed, Embase, Cochrane Library, and other databases were searched. Pairs of reviewers identified RCTs that compared levosimendan and placebo or other therapies, and the results reported AF events data. Random effects models were used (at a significance level of 5%). Results Twenty-nine eligible trials comprising 6550 participants were included, eleven of which evaluated the non-postoperative AF incidence, and 18 included postoperative AF. The analysis revealed that levosimendan elevated the AF risk significantly in the non-postoperative group (OR, 1.62; 95% CI: 1.19-2.20; p=0.002) and reduced the AF incidence in the postoperative group (OR, 0.65; 95% CI: 0.44-0.96; p=0.03). AF occurrence decreased more significantly in patients who used levosimendan after cardiac surgery (OR, 0.53; 95% CI: 0.32-0.88; p=0.02) than in patients who used levosimendan before cardiac surgery (OR, 0.67; 95% CI: 0.42-1.06; p=0.09). Moreover, The AF risk was significantly elevated by levosimendan large bolus dose (bolus dose≥12 μg/kg) (OR, 1.44; 95% CI: 1.10-1.88; p=0.004) and decreased by small bolus dose of levosimendan (bolus dose<12 μg/kg) (OR, 0.64; 95% CI: 0.34-1.20; p=0.16). Conclusion Levosimendan was linked to an increased non-postoperative AF incidence. The employment of levosimendan was effective in preventing postoperative AF.

An Applied Anatomical Study on the Inferior Extensor Retinaculum of Ankle / Un Estudio de Anatomía Aplicada del Retináculo Extensor Inferior del Tobillo

SUMMARY: Through anatomical observations, the anatomical characteristics of the inferior extensor retinaculum of ankle (IER) of the ankle joint were elucidated, and its potential applications in treating lateral ankle instability or other conditions were discussed. A total of 12 adult foot specimens were dissected to expose the inferior extensor retinaculum of ankle, and a standard model was established. The pre-experimental scheme guided the recording of general findings, adjacent structures, lateral attachment in the tarsal sinus region, and influence on movement of inferior tendons. 1, attachment mean width: lateral band of IER 6.6±1.38 mm, oblique superomedial band of IER (32.3±3.97 mm), oblique inferomedial band of IER (30.0±5.30 mm) ; 2, mean length: lateral band of IER (78.1±4.20 mm) , oblique superomedial band of IER (14.2±0.80 mm), oblique inferomedial band of IER (71.8±2.61 mm); 3, maximum mean thickness: lateral band of IER (1.52±0.03 mm), oblique superomedial band of IER (0.89±0.05 mm), oblique inferomedial band of IER (0.73±0.16 mm); 4, the closest distance between IER and the tip of lateral malleolus: 23.9±0.83 mm; 5, mean width of the fiber tunnel:lateral fiber tunnel (11.9±1.16 mm), intermedium fiber tunnel (6.8±1.24 mm), medial fiber tunnel (8.6±0.79 mm); 6, mean distance from tunnel midpoint to lateral malleolar tip: lateral fiber tunnel (38.0±3.74 mm), intermedium fiber tunnel (69.8±4.15 mm), medial fiber tunnel (181.1±6.00 mm); 7, the distance between medial dorsal cutaneous nerve and the tip of lateral malleolus on the level of the IER (79.2±8.3 mm) the distance between intermediate cutaneous nerve of dorsum and the tip of lateral malleolus on the level of the IER (57.9±1.02 mm). The inferior extensor retinaculum of ankle is a crucial restraint unit of the anterior ankle tendon, and a comprehensive understanding of its anatomical characteristics holds significant implications for treating chronic ankle instability and exploring potential clinical applications.

A través de observaciones anatómicas, se dilucidaron las características anatómicas del retináculo extensor inferior (IER) de la articulación del tobillo y se discutieron sus posibles aplicaciones en el tratamiento de la inestabilidad lateral de esta articulación u otras afecciones. Se disecaron 12 muestras de pies de individuos adultos para exponer el retináculo extensor inferior del tobillo y se estableció un modelo estándar. El esquema preexperimental guió el registro de los hallazgos generales, las estructuras adyacentes, la inserción lateral en la región del seno tarsal y la influencia en el movimiento de los tendones inferiores. Se determino: 1. Ancho medio de inserción: banda lateral de IER (6,6 ± 1,38 mm), banda superomedial oblicua de IER (32,3 ± 3,97 mm), banda inferomedial oblicua de IER (30,0 ± 5,30 mm); 2. Longitud media: banda lateral de IER (78,1 ± 4,20 mm), banda superomedial oblicua de IER (14,2 ± 0,80 mm), banda inferomedial oblicua de IER (71,8 ± 2,61 mm); 3. Espesor medio máximo: banda lateral de IER (1,52 ± 0,03 mm), banda superomedial oblicua de IER (0,89 ± 0,05 mm), banda inferomedial oblicua de IER (0,73 ± 0,16 mm); 4. Distancia más próxima entre IER y el ápice del maléolo lateral: (23,9 ± 0,83 mm); 5.Ancho medio del túnel de fibra: túnel de fibra lateral (11,9 ± 1,16 mm), túnel de fibra intermedio (6,8 ± 1,24 mm), túnel de fibra medial (8,6 ± 0,79 mm); 6. Distancia media desde el punto medio del túnel hasta la punta del maléolor lateral: túnel de fibra lateral (38,0 ± 3,74 mm), túnel de fibra intermedio (69,8 ± 4,15 mm), túnel de fibra medial (181,1 ± 6,00 mm); 7. Distancia entre el nervio cutáneo dorsal medial y el a´pice del maléolo lateral en el nivel del IER (79,2 ± 8,3 mm); la distancia entre el nervio cutáneo intermedio dorsal y el ápice del maléolo lateral en el nivel del IER (57,9 ±1,02 mm). El retináculo extensor inferior del tobillo es una unidad de restricción crucial del tendón anterior del tobillo, y una comprensión integral de sus características anatómicas tiene implicaciones significativas para el tratamiento de la inestabilidad crónica del tobillo y la exploración de posibles aplicaciones clínicas.

Preliminary Study on Application of Combined Monitoring of Neuroelectrophysiology-Intracranial Pressure-Cerebral Perfusion Pressure in Craniotomy for Intracranial Aneurysm Clipping: An Anatomical and Clinical Study

SUMMARY: Intracranial aneurysm is a common cerebrovascular disease with high mortality. Neurosurgical clipping for the treatment of intracranial aneurysms can easily lead to serious postoperative complications. Studies have shown that intraoperative monitoring of the degree of cerebral ischemia is extremely important to ensure the safety of operation and improve the prognosis of patients. Aim of this study was to probe the application value of combined monitoring of intraoperative neurophysiological monitoring (IONM)-intracranial pressure (ICP)-cerebral perfusion pressure (CPP) in craniotomy clipping of intracranial aneurysms. From January 2020 to December 2022, 126 patients in our hospital with intracranial aneurysms who underwent neurosurgical clipping were randomly divided into two groups. One group received IONM monitoring during neurosurgical clipping (control group, n=63), and the other group received IONM-ICP-CPP monitoring during neurosurgical clipping (monitoring group, n=63). The aneurysm clipping and new neurological deficits at 1 day after operation were compared between the two groups. Glasgow coma scale (GCS) score and national institutes of health stroke scale (NIHSS) score were compared before operation, at 1 day and 3 months after operation. Glasgow outcome scale (GOS) and modified Rankin scale (mRS) were compared at 3 months after operation. All aneurysms were clipped completely. Rate of new neurological deficit at 1 day after operation in monitoring group was 3.17 % (2/63), which was markedly lower than that in control group of 11.11 % (7/30) (P0.05). Combined monitoring of IONM-ICP-CPP can monitor the cerebral blood flow of patients in real time during neurosurgical clipping, according to the monitoring results, timely intervention measures can improve the consciousness state of patients in early postoperative period and reduce the occurrence of early postoperative neurological deficits.

El aneurisma intracraneal es una enfermedad cerebrovascular común con alta mortalidad. El clipaje neuroquirúrgico para el tratamiento de aneurismas intracraneales puede provocar complicaciones posoperatorias graves. Los estudios han demostrado que la monitorización intraoperatoria del grado de isquemia cerebral es extremadamente importante para garantizar la seguridad de la operación y mejorar el pronóstico de los pacientes. El objetivo de este estudio fue probar el valor de la aplicación de la monitorización combinada de la monitorización neurofisiológica intraoperatoria (IONM), la presión intracraneal (PIC) y la presión de perfusión cerebral (CPP) en el clipaje de craneotomía de aneurismas intracraneales. Desde enero de 2020 hasta diciembre de 2022, 126 pacientes de nuestro hospital con aneurismas intracraneales que se sometieron a clipaje neuroquirúrgico se dividieron aleatoriamente en dos grupos. Un grupo recibió monitorización IONM durante el clipaje neuroquirúrgico (grupo de control, n=63) y el otro grupo recibió monitorización IONM-ICP-CPP durante el clipaje neuroquirúrgico (grupo de monitorización, n=63). Se compararon entre los dos grupos el recorte del aneurisma y los nuevos déficits neurológicos un día después de la operación. La puntuación de la escala de coma de Glasgow (GCS) y la puntuación de la escala de accidentes cerebrovasculares de los institutos nacionales de salud (NIHSS) se compararon antes de la operación, 1 día y 3 meses después de la operación. La escala de resultados de Glasgow (GOS) y la escala de Rankin modificada (mRS) se compararon 3 meses después de la operación. Todos los aneurismas fueron cortados por completo. La tasa de nuevo déficit neurológico 1 día después de la operación en el grupo de seguimiento fue del 3,17 % (2/63), que fue notablemente inferior a la del grupo de control del 11,11 % (7/30) (P 0,05). La monitorización combinada de IONM-ICP-CPP puede controlar el flujo sanguíneo cerebral de los pacientes en tiempo real durante el corte neuroquirúrgico; de acuerdo con los resultados de la monitorización, las medidas de intervención oportunas pueden mejorar el estado de conciencia de los pacientes en el período postoperatorio temprano y reducir la aparición de problemas postoperatorios tempranos y déficits neurológicos.

Comparison of Vertebral Artery Ultrasound, Magnetic Resonance Angiography and Digital Subtraction Angiography in the Diagnosis of Vertebral Artery Stenosis in Patients with Posterior Circulation Ischemia

SUMMARY: The aim of this study was to compare the clinical value of vertebral artery ultrasound (VAU), Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA) on vertebral artery stenosis in patients with posterior circulation ischemia. Seventy-three patients with posterior circulation ischemia underwent vertebral artery ultrasound and magnetic resonance angiography as well as digital subtraction angiography, and the diagnosis of vertebral artery stenosis (VAS) and the degree of stenosis (normal, mild stenosis, moderate stenosis, severe stenosis, and occlusion) were recorded and compared between digital subtraction angiogram and vertebral artery ultrasound and magnetic resonance angiography. The vertebral artery stenosis rates on digital subtraction angiography and vertebral artery ultrasound were 87.30 % (55/63) and 49.20 % (31/63), respectively, and the difference was statistically significant. The rates of vertebral artery stenosis on digital subtraction angiography and, magnetic resonance angiography was 90.38 % (47/52) and 88.46 % (46/ 52), respectively, and the differences was not statistically significant. The sensitivity, accuracy, negative predictive value, and positive predictive value of vertebral artery ultrasound in diagnosing vertebral artery stenosis were 51.35 %, 54.76 %, 18.18 %, and 95.00 %, respectively, lower than those of magnetic resonance angiography, which were 91.89 %, 90.48 %, 57.14 %, and 97.14 %, respectively. Of the noninvasive imaging techniques, vertebral artery ultrasound does not accurately characterize vertebral artery stenosis and its degree of stenosis. Magnetic resonance angiography effectively screens for vertebral artery stenosis and its degree of stenosis, and can be used as a reliable tool for vertebral artery stenosis in posterior circulation cerebral infarction, and can be used in conjunction with digital subtraction angiogram in order to improve diagnostic convenience and accuracy.

El objetivo de este estudio fue comparar el valor clínico de la ecografía de la arteria vertebral (VAU), la angiografía por resonancia magnética (ARM) y la angiografía por sustracción digital (DSA) en la estenosis de la arteria vertebral en pacientes con isquemia de la circulación posterior. A 73 pacientes con isquemia de la circulación posterior se les realizó una ecografía de la arteria vertebral y una angiografía por resonancia magnética, así como una angiografía por sustracción digital, y se les diagnosticó estenosis de la arteria vertebral (EVA) y el grado de estenosis (normal, estenosis leve, estenosis moderada, estenosis grave, y oclusión) se registraron y compararon la angiografía por sustracción digital y la ecografía de la arteria vertebral y la angiografía por resonancia magnética. Las tasas de estenosis de la arteria vertebral en la angiografía por sustracción digital y la ecografía de la arteria vertebral fueron del 87,30 % (55/63) y del 49,20 % (31/63), respectivamente, y la diferencia fue estadísticamente significativa. Las tasas de estenosis de la arteria vertebral en la angiografía por sustracción digital y la angiografía por resonancia magnética fueron del 90,38 % (47/52) y del 88,46 % (46/52), respectivamente, y las diferencias no fueron estadísticamente significativas. La sensibilidad, precisión, valor predictivo negativo y valor predictivo positivo de la ecografía de la arteria vertebral en el diagnóstico de estenosis de la arteria vertebral fueron 51,35 %, 54,76 %, 18,18 % y 95,00 %, respectivamente, inferiores a los de la angiografía por resonancia magnética, que fueron 91,89 %, 90,48 %, 57,14 % y 97,14 %, respectivamente. De las técnicas de imagen no invasivas, la ecografía de la arteria vertebral no caracteriza con precisión la estenosis de la arteria vertebral y su grado de estenosis. La angiografía por resonancia magnética detecta eficazmente la estenosis de la arteria vertebral y su grado de estenosis, y puede usarse como una herramienta confiable para la estenosis de la arteria vertebral en el infarto cerebral de circulación posterior, y puede ser utilizada junto con la angiografía por sustracción digital para mejorar el diagnóstico y la exactitud.

Acteoside Attenuates Recognition Memory Impairment in CUMS Rats via Regulating Synaptic Plasticity and mTOR Signaling Pathway / El Acteoside Atenúa el Deterioro de la Memoria de Reconocimiento en Ratas ELCI Mediante la Regulación de la Plasticidad Sináptica y la Vía de Señalización mTOR

SUMMARY: We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and p- P70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression.

Evaluamos el papel y el mecanismo del acteoside en la regulación del deterioro de la memoria inducido por estrés leve crónico impredecible (ELCI). Se utilizó ELCI para inducir depresión en ratas y el establecimiento exitoso del modelo ELCI se verificó mediante una prueba de natación forzada y una prueba de preferencia de sacarosa. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos evaluaron las funciones de la memoria. Los cambios estructurales en la corteza y el hipocampo se observaron mediante tinción con hematoxilina y eosina (HE). La tinción por inmunofluorescencia y la transferencia Western determinaron los niveles de proteína. La prueba del laberinto en Y y la prueba de reconocimiento de objetos novedosos mostraron que había un deterioro del rendimiento de la memoria en ratas del grupo ELCI, que mejoró con el tratamiento con acteósidos. La tinción con HE mostró que la exposición a ELCI dañó la estructura de la corteza y el hipocampo, mientras que el tratamiento con actósidos alivió los cambios estructurales. En comparación con el grupo de control, los niveles de BNDF y CREB en la corteza y el hipocampo del grupo ELCI disminuyeron significativamente. Acteoside revirtió significativamente las expresiones de estas proteínas en ratas ELCI. Mientras tanto, en comparación con el grupo control, los niveles de p-mTOR y p-P70S6K en la corteza y el hipocampo del grupo ELCI aumentaron significativamente, y estos cambios fueron revertidos significativamente ELCI por el acteoside. Sin embargo, el efecto del acteoside sobre la señalización de mTOR fue notablemente bloqueado por la rapamicina, un inhibidor específico de la señalización de mTOR. El acteoside puede atenuar el deterioro de la memoria y mejorar el daño neuronal y la plasticidad sináptica en ratas con depresión, probablemente mediante la inhibición de la vía de señalización mTOR. Acteoside puede servir como un reactivo novedoso para la prevención de la depresión.

PITPNA-AS1 Inhibits Cell Proliferation and Migration in Ovarian Cancer by Regulating the MIR-223-3p/RHOB Axis

ABSTRACT Background: Ovarian cancer is a fatal gynecologic malignancy. Long non-coding RNA (lncRNA) has been verified to serve as key regulator in ovarian cancer tumorigenesis. Objective: The aim of the study was to study the functions and mechanism of lncRNA PITPNA-AS1 in ovarian cancer cellular process. Methods: Clinical ovarian cancer samples were collected and stored at an academic medical center. Cellular fractionation assays and fluorescence in situ hybridization were conducted to locate PITPNA-AS1 in OC cells. TUNEL staining, colony-forming assays, and Transwell assays were performed for evaluating cell apoptosis as well as proliferative and migratory abilities. Western blot was conducted for quantifying protein levels of epithelial-mesenchymal transition markers. The binding relation between genes was verified by RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays. Gene expression levels in ovarian cancer tissues and cells were subjected to RT-qPCR. Results: PITPNA-AS1 level was downregulated in ovarian cancer samples and cells. PITPNA-AS1 overexpression contributed to the accelerated ovarian cancer cell apoptosis and inhibited cell migration, proliferation, and epithelial-mesenchymal transition process. In addition, PITPNA-AS1 interacted with miR-223-3p to regulate RHOB. RHOB knockdown partially counteracted the repressive impact of PITPNA-AS1 on ovarian cancer cell activities. Conclusion: PITPNA-AS1 inhibited ovarian cancer cellular behaviors by targeting miR-223-3p and regulating RHOB. (Rev Invest Clin. 2024;76(2):103-15)

Prediction of Prognostic Features Based on Neutrophil-Related Genes for Lung Squamous Cell Carcinoma Reveals Immune Landscape and Drug Candidates

ABSTRACT Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31)

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Correlation analysis between peripheral blood dendritic cell subsets and PD-1 in patients with peritoneal adenocarcinoma

Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma.

Safety of a 90-min duration of intravenous infusion of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma in a tertiary hospital in China: a prospective, open-label, exploratory clinical trial

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.

Serum autophagy-related gene 5 level in stroke patients: correlation with CD4+ T cells and cognition impairment during a 3-year follow-up

Abstract Autophagy-related gene (ATG) 5 regulates blood lipids, chronic inflammation, CD4+ T-cell differentiation, and neuronal death and is involved in post-stroke cognitive impairment. This study aimed to explore the correlation of serum ATG5 with CD4+ T cells and cognition impairment in stroke patients. Peripheral blood was collected from 180 stroke patients for serum ATG5 and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cell detection via enzyme-linked immunosorbent assays and flow cytometry. The Mini-Mental State Examination (MMSE) scale was completed at enrollment, year (Y)1, Y2, and Y3 in stroke patients. Serum ATG5 was also measured in 50 healthy controls (HCs). Serum ATG5 was elevated in stroke patients compared to HCs (P<0.001) and was positively correlated to Th2 cells (P=0.022), Th17 cells (P<0.001), and Th17/Treg ratio (P<0.001) in stroke patients but not correlated with Th1 cells, Th1/Th2 ratio, or Treg cells (all P>0.050). Serum ATG5 (P=0.037), Th1 cells (P=0.022), Th17 cells (P=0.002), and Th17/Treg ratio (P=0.018) were elevated in stroke patients with MMSE score-identified cognition impairment vs those without cognition impairment, whereas Th2 cells, Th1/Th2 ratio, and Treg cells were not different between them (all P>0.050). Importantly, serum ATG5 was negatively linked with MMSE score at enrollment (P=0.004), Y1 (P=0.002), Y2 (P=0.014), and Y3 (P=0.001); moreover, it was positively related to 2-year (P=0.024) and 3-year (P=0.012) MMSE score decline in stroke patients. Serum ATG5 was positively correlated with Th2 and Th17 cells and estimated cognitive function decline in stroke patients.