Hospitalizaciones evitables por problemas de salud sensibles a cuidados ambulatorios: construcción y validación de la lista Uruguaya de patologías

Introducción: Las hospitalizaciones por Ambulatory Care Sensitive Conditions es un indicador que mide la utilización de los servicios hospitalarios por problemas de salud que podrían haber sido prevenidos en el primer nivel de atención. El concepto se refiere a los procesos en que la atención ambulatoria efectiva puede ayudar a disminuir los riesgos de hospitalización, en un segundo nivel de atención. El objetivo del estudio fue construir y validar una lista uruguaya de problemas de salud sensibles a cuidados ambulatorios (PSSCA) según CIE-10. Metodología: Para la construcción de la lista inicial de códigos de PSSCA se realizó una revisión de los listados existentes y se propuso un listado inicial que fue validado a través del Método Delphi. Se propone un listado de 99 códigos diagnósticos de PSSCA adaptado a nuestro entono sanitario. Los mismos permiten identificar y cuantificar problemas de salud que pueden producir hospitalizaciones potenciamente evitables mediante cuidados ambulatorios accesibes y oportunos en el primer nivel de atención. Resultados: Se conformó un panel de 12 expertos. A partir de los datos obtenidos, considerando los 99 diagnósticos clasificados por CIE-10, éstos se pueden subclasificar en función de si la patología es infecciosa o no, obteniendo un resultado general de 62 patologías en un total de 99 que pueden ser clasificadas como infecciosas, lo que se corresponde a un 62 %. Discusión: De la comparación de la lista uruguaya de PSSCA a la que hemos arribado y las listas validadas utilizadas para la construcción inicial del listado de patologías propuesto, podemos decir que la primera presenta un mayor porcentaje de coincidencia con la lista de patologías de Bello Horizonte. Podemos mencionar que la mayoría de los problemas de salud identificados con base en el listado de PSSCA, son sensibles de ser resueltos con la atención primaria oportuna y de calidad que podría evitar o disminuir de una manera significativa su hospitalización. Conclusiones: Este trabajo describe el proceso de construcción y validación de una lista de códigos de PSSCA adaptados al contexto uruguayo a través del método Delphi. Hemos arribado a un listado que comprende un total de 99 diagnósticos, agrupadas en un total de diecinueve categorías que considera la especificidad del contexto uruguayo del indicador.

Introduction: Hospitalizations for Ambulatory Care Sensitive Conditions is an indicator that measures the use of hospital services for health problems that could have been prevented at the first level of care. The concept refers to the processes in which effective outpatient care can help reduce the risks of hospitalization, at a second level of care. The objective of the study was to build and validate a Uruguayan list of health problems sensitive to outpatient care (PSS-CA) according to ICD-10. Methodology: To construct the initial list of PSSCA codes, a review of the existing lists was carried out and an initial list was proposed that was validated through the Delphi Method. A list of 99 PSSCA diagnostic codes adapted to our healthcare environment is proposed. They make it possible to identify and quantify health problems that can lead to potentially avoidable hospitalizations through accessible and timely outpatient care at the first level of care. Results: A panel of 12 experts was formed. From the data obtained, considering the 99 diagnoses classified by ICD-10, these can be subclassified depending on whether the pathology is infectious or not, obtaining a general result of 62 pathologies in a total of 99 that can be classified as infectious, which corresponds to 62%. Discussion: From the comparison of the Uruguayan list of PSSCA that we have arrived at and the validated lists used for the initial construction of the proposed list of pathologies, we can say that the first presents a higher percentage of coincidence with the list of pathologies of Bello Horizonte . We can mention that most of the health problems identified based on the PSSCA list are sensitive to being resolved with timely and quality primary care that could prevent or significantly reduce hospitalization. Conclusions: This work describes the process of construction and validation of a list of PSSCA codes adapted to the Uruguayan context through the Delphi method. We have arrived at a list that includes a total of 99 diagnoses, grouped into a total of nineteen categories that consider the specificity of the Uruguayan context of the indicator.

Introdução: As Internações por Condições Sensíveis à Atenção Ambulatorial são um indicador que mede a utilização de serviços hospitalares para problemas de saúde que poderiam ter sido evitados no primeiro nível de atenção. O conceito refere-se aos processos em que um atendimento ambulatorial eficaz pode auxiliar na redução dos riscos de internação, em um segundo nível de atenção. O objetivo do estudo foi construir e validar uma lista uruguaia de problemas de saúde sensíveis à atenção ambulatorial (PSS-CA) segundo a CID-10. Metodologia: Para construir a lista inicial de códigos PSSCA foi realizada uma revisão das listas existentes e foi proposta uma lista inicial que foi validada através do Método Delphi. É proposta uma lista de 99 códigos de diagnóstico PSSCA adaptados ao nosso ambiente de saúde. Permitem identificar e quantificar problemas de saúde que podem levar a hospitalizações potencialmente evitáveis ​​através de cuidados ambulatórios acessíveis e oportunos no primeiro nível de cuidados. Resultados: Foi formado um painel de 12 especialistas. A partir dos dados obtidos, considerando os 99 diagnósticos classificados pela CID-10, estes podem ser subclassificados consoante a patologia seja infecciosa ou não, obtendo-se um resultado geral de 62 patologias num total de 99 que podem ser classificadas como infecciosas, o que corresponde para 62%. Discussão: A partir da comparação da lista uruguaia de PSSCA a que chegamos e das listas validadas utilizadas para a construção inicial da lista de patologias proposta, podemos dizer que a primeira apresenta um maior percentual de coincidência com a lista de patologias de Belo Horizonte. Podemos mencionar que a maioria dos problemas de saúde identificados com base na lista PSSCA são sensíveis para serem resolvidos com cuidados primários oportunos e de qualidade que possam prevenir ou reduzir significativamente a hospitalização. Conclusões: Este trabalho descreve o processo de construção e validação de uma lista de códigos PSSCA adaptados ao contexto uruguaio através do método Delphi. Chegamos a uma lista que inclui um total de 99 diagnósticos, agrupados em um total de dezenove categorias que consideram a especificidade do contexto uruguaio do indicador.

Protocolo de validación del instrumento Examen Dental Preventivo del Adulto Mayor

Los desafíos del envejecimiento de la población y la acumulación de daño oral nos obligan a desarrollar herramientas diagnosticas validas y confiables que nos permitan caracterizar a la población, evaluar sus necesidades terapéuticas, planificar intervenciones significativas y realizar seguimiento de su condición. Con este propósito realizamos una revisión sistemática de la literatura relevante para establecer una metódica secuencial para la validación de la herramienta diagnostica Examen Dental Preventivo del Adulto Mayor. Seleccionamos 48 artículos relevantes, cuya heterogeneidad impidió la realización de un metaanálisis. Sin embargo, los artículos seleccionados fueron sometidos a una síntesis cuantitativa analítica, que nos permitió identificar los dominios y estrategias relevantes para la validación y proponer un protocolo de cinco fases secuenciales que presentamos en extenso en el presente artículo.

The challenges of population aging and the accumulation of oral damage force us to develop valid and reliable diagnostic tools to characterize the population, evaluate their therapeutic needs, plan significant interventions, and monitor their condition post treatment. We carried out a systematic review of the relevant literature to establish a sequential method for the validation of the Preventive Dental Examination of the Elderly diagnostic tool. We selected 48 relevant articles, whose heterogeneity prevented us from performing a meta-analysis. However, the selected articles were subjected to an analytical quantitative synthesis, which allowed us to identify the relevant domains and strategies for validation and then propose a protocol of five sequential phases that we present in detail in this article.

Avaliação da amamentação com emprego da escala latch em um hospital público do Distrito Federal / Assessment of breastfeeding using the latch scale in a public hospital in the Federal District

Avaliar o processo de amamentação em um hospital da rede pública do Distrito Federal através da aplicação da escala LATCH. Método: Trata-se de um estudo epidemiológico, observacional, descritivo, transversal, de abordagem quantitativa. Resultados: Ao aplicar a escala LATCH para avaliação do aleitamento materno observou-se uma inclinação ascendente dos escores no decorrer do período pós-parto. Foram identificadas evoluções nas variáveis pega, deglutição audível e colo. O tipo de mamilo não apresentou grandes diferenças entre os grupos, sendo o protuso o tipo mais comum. O conforto apresentou uma evolução inversamente proporcional ao longo do tempo. Conclusão: A escala LATCH permite aos profissionais dos setores materno-infantis sistematizar o cuidado em amamentação de forma direcionada e facilitada, sendo um importante instrumento de avaliação no ambiente intra hospitalar.(AU)

To evaluate the breastfeeding process in a public hospital in the Federal District by applying the LATCH scale. Method: This is an epidemiological, observational, descriptive, cross-sectional study with a quantitative approach. Results: When applying the LATCH scale to assess breastfeeding, an upward slope of the scores was observed over the course of the postpartum period. Developments were identified in the latch-on, audible swallowing and lap variables. The type of nipple did not differ greatly between the groups, with protrusion being the most common type. Comfort showed an inversely proportional evolution over time. Conclusion: The LATCH scale allows professionals in the maternal and child sectors to systematize breastfeeding care in a targeted and facilitated way, making it an important assessment tool in the intra-hospital environment.(AU)

Evaluar el proceso de amamantamiento en un hospital público del Distrito Federal mediante la aplicación de la escala LATCH. Método: Se trata de un estudio epidemiológico, observacional, descriptivo, transversal, con abordaje cuantitativo. Resultados: Al aplicar la escala LATCH para evaluar la lactancia materna, se observó una pendiente ascendente de las puntuaciones en el transcurso del puerperio. Se identificaron evoluciones en las variables prensión, deglución audible y regazo. El tipo de pezón no presentó grandes diferencias entre los grupos, siendo el más frecuente el protruido. La comodidad mostró una evolución inversamente proporcional a lo largo del tiempo. Conclusión: La escala LATCH permite a los profesionales del sector materno-infantil sistematizar la atención a la lactancia materna de forma dirigida y facilitada, lo que la convierte en una importante herramienta de evaluación en el ámbito intrahospitalario.(AU)

Mecanismos de pago en salud: resultados de ejecución del pago asociado a diagnóstico en cirugía bariátrica en su primer año de implementación en Chile / Healthcare payment mechanism: Execution results of bundled payment program for bariatric surgery diagnosis in its first year of implementation in Chile

Introducción Más de 600 mil personas en Chile viven con obesidad mórbida. La incorporación de intervenciones terapéuticas eficaces, seguras y costo-efectivas es crítica para los sistemas de salud y esquemas de aseguramiento. En el año 2022 se incorporaron al arancel de modalidad de libre elección del Fondo Nacional de Salud dos códigos de pago asociado a diagnóstico para cirugía bariátrica: gástrico y manga gástrica. El objetivo fue caracterizar la ejecución del programa de mecanismo de pago tipo pago asociado a diagnóstico de cirugía bariátrica en su primer año de implementación. Métodos Estudio descriptivo y observacional de abordaje pragmático de la ejecución nacional del pago asociado a diagnóstico en cirugía bariátrica. Se examinaron variables de caracterización sociodemográfica (sexo, tramos etarios y tramos del Fondo nacional de Salud) y caracterización de cirugías según código desagregadas por prestador público o privado, periodo de emisión, gasto unitario, copago, y préstamos médicos, entre marzo y diciembre de 2022. Resultados Se registraron n = 13 118 cirugías (45,81% versus 54,19% manga), de las cuales n = 2424 (18,48%) emplearon préstamos médicos. Un 85,01% (p = 0,01) de los procedimientos fueron en mujeres; en personas entre 35 y 39 años (20,15%); y 45,12% en beneficiarios del tramo B. El 99,21% de las cirugías se realizó en prestadores privados. Diez de estos concentraron el 50% de la actividad (rango n = 1200 a 426 cirugías anuales; n = 4,8 a 1,7 cirugías por día hábil). El gasto total del programa fue $71 626 948 350 CLP, explicando un 5,04% de la actividad total del Programa nacional de Pago Asociado a Diagnóstico. Conclusiones La implementación de este bono para cirugía bariátrica benefició a más de 13 mil personas que viven con obesidad, mayormente mujeres, en edades productivas, y con capacidad de compra. Como estrategia de equidad, independientemente de la vía de acceso mediante el bono, será importante cautelar la actividad en la red pública.

Introduction More than 600 thousand people in Chile live with morbid obesity. Effective, safe, cost-effective therapeutic interventions are critical for healthcare systems and insurance schemes. In 2022, two bundled payment codes for bariatric surgery (gastric bypass and gastric sleeve) were incorporated into the National Health Fund's free-choice modality fee scheme. The objective was to characterize the execution of this payment mechanism program associated with bariatric surgery diagnosis in its first year of implementation.More than six hundred thousand people in Chile are estimated to live with morbid obesity. Effective, safe, cost-effective therapeutic interventions are critical for health systems and insurance schemes. In 2022, FONASA incorporated two Bariatric Surgery codes into the Free Choice Modality: Gastric Bypass and Sleeve Gastrectomy. Our objective was to characterize the execution of the Bariatric Surgery Bundled Payment Program in its first year of implementation. Methods Descriptive and observational study of the pragmatic approach of the national execution of the payment associated with diagnosis in bariatric surgery. We examined sociodemographic variables (sex, age brackets, and National Health Fund tranches) and characterization of surgeries by code broken down by public or private provider, period of issue, unit cost, co-payment, and medical loans between March and December 2022. Results We recorded n = 13 118 surgeries (45.81% bypass versus 54.19% sleeve), of which n = 2424 (18.48%) used medical loans. A total of 85.01% (p = 0.01) of the procedures were in women, in people between 35 and 39 years of age (20.15%), and 45.12% in beneficiaries of tranche B. Private providers performed a total of 99.21% of the surgeries. Ten accounted for 50% of the activity (range n = 1200 to 426 surgeries per year; n = 4.8 to 1.7 surgeries per working day). Total program expenditure was $71 626 948 350 CLP, accounting for 5.04% of the total activity of the national Diagnosis Associated Payment Program. Conclusions The implementation of this bariatric surgery voucher benefited more than 13 thousand people living with obesity, mostly women of productive ages and with purchasing capacity. As an equity strategy, regardless of the access route through the voucher, it will be important to safeguard the activity in the public network.

Estimación del presupuesto de vacunas del PAI-Paraguay 2007-2022 y el impacto de posibles cambios

Introducción: el programa de vacunación es una intervención de salud pública cuyo propósito es controlar o eliminar enfermedades inmunoprevenibles. El objetivo de este trabajo fue estimar la evolución del presupuesto en vacunas entre 2007 y 2022, y el impacto de potenciales mejoras en el calendario de vacunaciones de Paraguay. Método: se estimó la evolución del presupuesto en vacunas según los cambios entre 2007 y 2022, y el impacto de esquemas alternativos versus el actual, que incluyen la vacuna contra la influenza cuádruple, séxtuple en lactantes, el agregado de la vacuna contra papiloma en varones y meningococo ACYW en adolescentes. La perspectiva del análisis fue la del Ministerio de Salud Pública y el horizonte temporal de un año. Los resultados de las alternativas se expresan como impacto presupuestal versus el año 2022. Resultados: entre 2007 y 2022 la cantidad de biológicos del Programa Ampliado de Inmunizaciones pasó de 11 a 18 e incorporó indicaciones de algunas vacunas. Se estima que el presupuesto se incrementó de 3,8 a 29,9 millones de dólares entre los extremos de la serie. Las alternativas implicarían un incremento de 13%, 35%, 5% y 10%, individualmente. El incremento en conjunto alcanza el 62%. Conclusiones: el aumento del gasto en vacunas fue de ocho veces entre 2007 y 2022. Se estima el impacto presupuestal en diferentes escenarios que se interpretan como mejoras comparadas con el actual de 2022, siendo el incremento más exigente de un 35%. La evidencia generada puede colaborar en el proceso de toma de decisiones acerca de esta política pública en Paraguay.

Introduction: the vaccination program is a public health intervention aimed at controlling or eliminating vaccine-preventable diseases. The objective of the study was to estimate the evolution of the vaccine budget between 2007 and 2022 and the impact of potential improvements in Paraguay's vaccination schedule. Method: the evolution of the vaccine budget was estimated considering the changes introduced between 2007 and 2022 and the impact of alternative schedules versus the current one. These alternatives include the addition of the quadrivalent influenza vaccine, the hexavalent vaccine for infants, the inclusion of the HPV vaccine for boys, and the ACYW meningococcal ACYW vaccine for adolescents. The analysis was conducted from the perspective of the Ministry of Health, with a time horizon of one year. The results of the alternatives are expressed as budget impact compared to the year 2022. Results: between 2007 and 2022, the number of biological products in the EPI increased from 11 to 18, and additional indications for some vaccines were incorporated. The budget is estimated to have increased from 3.8 to 29.9 million USD over the series. The alternatives would result in individual increases of 13%, 35%, 5%, and 10%. The combined increase reaches 62%. Conclusions: the increase in vaccine expenditure was eightfold between 2007 and 2022. The budget impact was estimated in different scenarios, interpreted as improvements compared to the current 2022 scenario, with the most demanding increase being 35%. The generated evidence can assist in the decision-making process regarding this public policy in Paraguay.

Introdução: o programa de vacinação é uma intervenção de saúde pública cuja finalidade é controlar ou eliminar doenças imunopreveníveis. O objetivo deste estudo foi estimar a evolução do orçamento de vacinas entre 2007 e 2022 e o impacto de possíveis melhorias no cronograma de vacinação do Paraguai. Métodos: estimamos a evolução do orçamento de vacinas de acordo com as mudanças ocorridas entre 2007 e 2022 e o impacto de esquemas alternativos em relação ao atual, que incluem a vacina quádrupla contra a gripe, a sextupla em bebês, a adição da vacina contra o papilomavírus em homens e a vacina meningocócica ACYW em adolescentes. A perspectiva da análise foi a do Ministerio de Salud e o intervalo de tempo foi de um ano. Os resultados das alternativas são expressos como impacto orçamentário em relação a 2022. Resultados: Entre 2007 e 2022, o número de produtos biológicos do PAI aumentou de 11 para 18 e incorporou indicações para algumas vacinas. Estima-se que o orçamento tenha aumentado de US$ 3,8 milhões para US$ 29,9 milhões entre os extremos da série. As alternativas implicariam em um aumento de 13%, 35%, 5% e 10% individualmente. O aumento geral chega a 62%. Conclusões: o aumento nos gastos com vacinas foi de oito vezes entre 2007-2022. O impacto orçamentário é estimado em diferentes cenários que são interpretados como melhorias em comparação com o cenário de 2022, sendo que o aumento mais exigente é de 35%. As evidências geradas podem contribuir para o processo de tomada de decisão relacionado a essa política pública no Paraguai.

The Catalytic Mechanism and Activity Modulation of Manganese Superoxide Dismutase / 生物化学与生物物理进展

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Protein Modification Omics： A Novel Approach Investigating Mechanisms of Chinese Medicines / 中国实验方剂学杂志

Traditional Chinese medicine （TCM）， as an invaluable scientific legacy and cultural patrimony of China， encapsulates the cumulative wisdom of millennia from the Chinese civilization. The deeply rooted medical theories and extensive empirical practices of TCM hold an indispensible central role within China's healthcare framework. Facing the challenges of modern medicine and health needs， it is particularly urgent to explore the mechanisms of Chinese medicines. Post-translational modification （PTM）， as a core mechanism to regulate the complex and diverse protein functions， is a bridge between environmental stimuli and physiological responses. Different PTMs can interact with each other to form a complex regulatory network， which is in line with the multi-component and multi-target action of Chinese medicines. In recent years， protein modification omics has emerged as a powerful means to probe into PTMs， and studies have employed protein modification omics to investigate the mechanisms of Chinese medicines. However， the research in this field is still in the initial stage. This article summarizes the basic theory of PTM and the basic research process of protein modification omics， reviews the application status of protein modification omics in the research on the mechanisms of Chinese medicines， and analyzes the existing research limitations. This study aims to explore an innovative research paradigm for analyzing the mechanisms of Chinese medicines from the perspective of PTM and provide a theoretical basis and practical guidance for understanding the mechanisms of Chinese medicines in the future.

Zhuangtongyin Modulates Ferroptosis via the Nrf2-SCL7A11/xCT-Gpx4 Pathway to Improve Cerebral Ischemia-reperfusion Injury / 中山大学学报(医学科学版)

ObjectiveTo investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion （MCAO） model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism. MethodsC57BL/6J mice were randomly divided into Sham operation group （Sham）， model group （MCAO）， low-dose Zhuangtongyin group （ZTY-L）， high-dose Zhuangtongyin group（ZTY-H）， with 5 mice in each group. The MCAO group was modelled by silica gel embolization， the middle cerebral artery of mice was embolized for 1h， then the silica gel was pulled out and reperfusion was performed after 72 h； and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted. The neural function of mice was evaluated by Zea-Longa method. TTC staining was used to evaluate the volume of cerebral infarction. The level of brain injury was evaluated by HE staining and Nissl staining. Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain. The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR， and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain. The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR. The expressions of Nrf2， SCL7A11/xCT， Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence. ResultsZhuangtongyin improved the nerve function of mice after MCAO （P＜0.05） and the cerebral infarction volume of mice （P＜0.05） and alleviate the pathological injury of cerebral cortex cells after MCAO operation. Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO. Additionally， Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA （P＜0.001）， a transporter associated with cellular iron ion uptake， in the brains of post-MCAO mice. Furthermore， Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE （P＜0.001） and suppressed ACSL4 mRNA expression in brain tissue post-MCAO （P＜0.001）. Besides， Zhuangtongyin downregulated the expression of PTGS2 mRNA （P＜0.001）， in the brains of post-MCAO mice. Zhuangtongyin increased the expression of nrf2 into the nucleus （P＜0.001）， and increased the expression of xCT and Gpx4 in neurons after MCAO （P＜0.001）. ConclusionZhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice， alleviate the pathological damage of cerebral cortex cells， and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway. Therefore， it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.

Mechanism of telomerase in affecting biological characteristics of gastric cancer / 国际外科学杂志

Gastric cancer is one of the major diseases threatening human health, with a high incidence and a low early diagnostic rate. There are many bottlenecks encountered during its treatment. Consequently, improving the early diagnostic rate and exploring new therapeutic targets are currently urgent challenges that need to be addressed. Telomerase is undetectable in normal tissues, but it exhibits high specificity and sensitivity in most cancers and has a definite correlation with prognosis. It may serve as a serum tumor marker and prognostic indicator. Human telomerase reverse transcriptase (hTERT) gene polymorphism can regulate the susceptibility of people to gastric cancer, and affect the occurrence, development, proliferation and apoptosis of gastric cancer through its target gene. Substances such as resistin, visfatin, G-quadruplex and methylenedioxyaniline can affect the occurrence and development of gastric cancer by regulating telomerase expression. The mechanism by which hTERT regulates tumor invasion and metastasis is currently unclear, so elucidating its mechanism is of great significance.This paper will review the research progress of this mechanism in recent years.

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-l ,4-dione on resisting hepatic fibrosis induced by CC14 in rats and its mechanisms via TGF-pi/Smads signaling pathway / 中国药理学通报

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Investigating the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination in ameliorating psoriatic lesions / 中国药理学通报

Aim In this study, a mouse model of psoriasis-like lesions induced by 62. 5 mg imiquimod was used to explore the effect and mechanism of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for the topical treatment of psoriasis. Methods Firstly, the topical administration of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination for treating psoriasis in progressive and recurrent stages was evaluated by psoriatic mouse model and HE staining. Secondly, immunohistochemistry was used to study the regulatory effects of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination on the pivotal pathological mechanism of psoriasis-the positive feedback loop between the abnormal proliferation of keratinocytes and skin immune microenvironment. Finally, metabolomics technology was used to explore whether Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae combination topically treat psoriasis by regulating inflammation-related metabolism and lipid metabolism pathways. Results The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae alleviated psoriasis-like lesions in mice. It effectively relieved the recurrence after the cure of psoriatic lesions in mice, and the efficacy is comparable to that of benweimod. The combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae inhibited the proliferation of mouse epidermal keratinocytes and reduced the number of T cells in the skin. The potential molecular mechanism was that the combination of Sophorae Flavescentis Radix and Rhizoma Smilacis Glabrae regulated arachidonic acid metabolism, sphin- golipid metabolism, tryptophan metabolism and phenylalanine metabolism. Conclusions The combination of Sophora Flavescens Radix and Rhizoma Smilacis Glabrae can relieve psoriasis-like lesions in mice by inhibiting the proliferation of epidermal keratinocytes and reducing the number of T cells in the skin and regulating metabolism to intervene psoriasis recurrence. This study provides a potential topical drug of psoriasis for relieving psoriasis recurrence.

Research progress on drug treatment and drug resistance mechanism of gastrointestinal stromal tumors / 中国临床药理学与治疗学

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Study on mechanism and Huanglong Mixture in the treatment of children with cough variant asthma and experimental verification based on network pharmacologic analysis / 国际中医中药杂志

Objective:To study the the mechanism of action of Huanglong Mixture in the treatment of cough variant asthma (CVA) in children based on the IL-4/signal transduction and activator of transcription 6 (STAT6) signaling pathway using network pharmacology methods, molecular docking techniques, and in vitro cell experiments.Methods:The components and targets of various TCM components in Huanglong Mixture were searched in TCMSP database, HERB database and literature, and the disease targets of CVA were found in Gene Cards database, OMIM database, DrugBank database and PharmGkb database. The STRING database was used to construct the protein-protein interaction network, and Cytoscape 3.9.1 was used for topology analysis to screen out the core targets. The disease-drug-component-target network was constructed to screen out the core components. The KEGG enrichment analysis and GO enrichment analysis of the intersection targets were performed using Metascape software. PDB protein database, PubChem, Autodock and R language were used for molecular docking verification of core targets and core drug components. Finally, rat primary airway smooth muscle cells were cultured, modeled with interleukin-4 (IL-4), and p-STAT6 expression in the cytoplasm and nucleus was detected by Western blot.Results:A total of 122 effective components were obtained, including quercetin, kaempferol, luteolin and so on. The core targets included JUN, ESR1, TP53, MYC, HIF1, etc. GO enrichment analysis involved biological processes such as response to external stimuli, response to oxygen levels, positive regulation of protein phosphorylation, and regulation of cellular stress response. KEGG enrichment analysis showed that the main pathways of Huanglong Mixture in treating CVA included advanced glycation end product-glycation end product receptor (AGE-RAGE) signaling pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Janus kinase/signal transduction activation factor (JAK-STAT) signaling pathway. Molecular docking found that the core targets and core drug components had good combination. Cell experiments also confirmed that Huanglong Mixture could inhibit p-STAT6 entering the nucleus.Conclusions:The effective components and targets of Huanglong Mixture in the treatment of CVA are successfully predicted. The mechanism of Huanglong Mixture in the treatment of children with CVA may be related to the inhibition of IL-4/STAT6 signaling pathway.

Exploring mechanism of Huayu Pills combined with immunocheckpoint inhibitors in treating triple-negative breast cancer based on network pharmacology / 国际中医中药杂志

Objective:To explore the potential mechanism of Huayu Pills in the treatment of TNBC (triple-negative breast cancer) using network pharmacology.Methods:TCMSP (Traditional Chinese Medicine Systems Pharmacology), PubChem, STITCH and SwissTargetPrediction databases were used to analyze the potential targets of Huayu Pills. TNBC disease targets were screened based on the TCGA (The Cancer Genome Atlas) database. The drug-disease mapping target was constructed by PPI network, key target screening and module analysis, and the DAVID database was used for GO function annotation and KEGG signal pathway enrichment analysis. SD rats were orally administered 3.94 g/kg of Huayu Pills decoction for 4 days to prepare medicated serum. HUVEC cells were randomly divided into a control group and an experimental group using a random number table method. The experimental group received intervention with Huayu Pills containing serum for 24 hours, inoculated in matrigel's solidified 48 well plate and HUVEC angiogenesis was observed 3 hours later.Results:130 possible targets of Huayu Pills in the treatment of TNBC were obtained. VEGFA is the core target. The cascade of angiogenesis, hypoxia, and blood coagulation may be the main functions and key signals of Huayu Pills in the treatment of TNBC. In vitro studies have shown that serum containing Huayu Pills can promote the normalization of tumor blood vessels in HUVEC cells.Conclusion:Huayu Pills may promote tumor vascular normalization (angiogenesis, hypoxia, coagulation cascade reactions) through VEGF targets, and can assist immune checkpoint inhibitors in the treatment of TNBC.

Current research on driving fatigue induced by special vehicles / 军事医学

Fatigue-related traffic accidents and fatalities have been extensively studied by scholars globally.Specialized vehicles,due to their unique mission profiles,are more likely to cause driving-related fatigue and serious consequences.This paper reviews the current research of fatigue driving by using an inductive analysis method to summarize the mechanisms,risk factors,and monitoring methods.This paper also offers a vision of priorities and methodologies for research in the future.It is recommended that the mechanisms of driving fatigue be explored at the molecular biological level and that fatigue monitoring systems be made more feasible via the combined application of non-intrusive monitoring in order to reduce the toll on life and property taken by driving fatigue.

Research Progress in Tong Du Tiao Shen of Mental Disorders / 世界科学技术-中医药现代化

Mental disorders are characterized by disturbances in behavior,volition,emotion,and cognition and are considered emotional diseases in traditional Chinese medicine.Acupuncture is one of the most widely used complementary alternative therapies for the treatment of mental disorders.Recently,there has been growing interest in the use of the Tong Du Tiao Shen(Dredging Du meridian to regulate the spirit)as a primary treatment.However,a comprehensive summary of the establishment and related acupuncture methods of Tong Du Tiao Shen is lacking.This paper aims to address this gap by exploring the origin and development of Tong Du Tiao Shen,its application in treating mental disorders,and the modern biological mechanisms involved.Ultimately,this paper seeks to expand the clinical application of Tong Du Tiao Shen acupuncture and provide a scientific basis for future research in this field.

Transcriptome Data and Comparative Medical Analysis of COVID-19 Virus Infection / 实验动物与比较医学

ObjectiveTo provide more basic information of comparative medicine for the study of biological changes and pathogenesis of COVID-19 by systematical sorting and analyzing the transcriptome data.MethodsFollowing a retrieval strategy, using COVID-19 and SARS-CoV-2 as key words, transcriptome datasets related to COVID-19 from January 2020 to May 2023 were collected from GEO, ArrayExpress and GEN Transcriptome databases. The composition, distribution, and research application of COVID-19 transcriptome data resources were analyzed. Data distribution was visually displayed and correlation analysis was performed. The research applications and limitations of existing COVID-19 transcriptome data were analyzed from the perspectives of clinical medicine and comparative medicine, focusing on clinical-related molecular mechanisms, biomarkers and related immune responses, treatment intervention strategies, etc. The research value and application prospects were discussed.Results A total of 975 sets of COVID-19 transcriptome data were included. Among three databases, datasets from humans accounted for the highest proportion, namely 71.9%, 77.9%, and 90%, respectively. Species other than humans, such as mice, were the main sources of data, with the respiratory and nervous systems having the highest distribution of data. Twenty-seven datasets were associated with clinical significance. Analysis revealed that respiratory tract injury and other related molecular mechanisms were obtained through transcriptome data mining. Biomarkers such as cfDNA could be used as therapeutic targets. The severity of COVID-19 infection was associated with cell changes and disorders represented by M1 macrophages. Comparative medical analysis showed that mice, hamsters, and other animals were susceptible to SARS-CoV-2. Rhesus monkeys and cynomolgus monkeys exhibited infection characteristics highly similar to human. Apart from respiratory symptoms, hamsters also exhibited digestive system symptoms. SARS-CoV-2 can replicate in the respiratory organs of various susceptible animals, the intestines of ferrets and the ears of minks, resulting in interstitial pneumonia, diffuse lung injury and other pathological changes of varying degrees. Based on the differences in immune responses, hamsters can be used for neutralizing antibody reaction research.Conclusion Currently there is a wealth of COVID-19 transcriptome data, but there is a lack of comparative transcriptome research. Transcriptomics can be combined with comparative medicine to further explore the differences in comparative medicine of COVID-19.

Analysis of the Current Status and Prospects of Multi-Omics Technologies in the Field of Traditional Chinese Medicine / 中医杂志

Due to the complexity of traditional Chinese medicine （TCM） interventions and the diversity of herbal components， single-omics technologies such as genomics， transcriptomics， proteomics， and metabolomics often cannot comprehensively elucidate the scientific connotations of TCM. Multi-omics technologies driven by system biology can analyze the theoretical connotations and application mechanisms of TCM from different levels such as genes， gene expression， proteins， and metabolites， in line with the holistic view of TCM， which helps to promote the modernization of TCM. By reviewing the literature on the application of omics technologies in the field of TCM， it is found that multi-omics technologies have been widely used in TCM for syndrome differentiation， evaluation of herbal quality， elucidation of pharmacological mechanisms， and drug toxicity assessment， providing comprehensive explanations of the mechanisms of action of TCM and overcoming the limitations of single-omics technologies， and having obtained significant achievements. However， multi-omics technologies also face challenges such as high cost， difficulties in data analysis due to large data volumes， and insufficient translation of research results. In the future， it is expected that through strengthening interdisciplinary cooperation， conducting long-term and dynamic clinical research， standardizing and normalizing data analysis processes， adopting appropriate and reasonable multi-omics integration patterns， establishing multi-omics databases for TCM， revealing the individualized characteristics， therapeutic mechanisms， and disease regulatory networks of TCM， the modernization of TCM will be promoted.

Research Progress on the Mechanisms of Berberine Protecting the Kidney in Diabetic Kidney Disease / 中山大学学报(医学科学版)

Diabetic kidney disease （DKD） is a chronic kidney disease caused by diabetes， influenced by genetic and environmental factors and their interaction. It is the primary cause of chronic kidney disease and end-stage renal disease. Recent studies have found， as a natural isoquinoline alkaloid， berberine （BBR） has hypoglycemic， hypolipidemic， antioxidant， anti-inflammatory and anti-fibrotic properties， thus protects against kidney injury in DKD. The mechanisms of action of BBR may involve improving glucolipid metabolism， reducing oxidative stress， alleviating inflammatory responses， mitigating renal fibrosis， regulating DNA methylation， promoting mitochondrial function and modulating the gut microbiota to enhance gut metabolism and clearance. This article systematically reviews the current status of research on the mechanisms of BBR in the treatment of DKD and provides reference for future clinical application of BBR in the treatment of DKD.

Research progress on targeted therapy and immunotherapy for esophageal cancer / 药学实践与服务

Esophageal cancer is a malignant tumor with high incidence and mortality rate in the world and its pathogenic factors are complex and diverse. There are no obvious symptoms in the early stage, and most patients are in the middle to late stage at the initial diagnosis. The prognosis of esophageal cancer is poor. The treatment mode of conventional surgical resection combined with chemoradiotherapy can no longer meet the current treatment needs of disease, and new treatment strategies are urgently needed. Molecular targeted therapy and immunotherapy are new treatment methods that have emerged in recent years, which have broken the therapeutic bottleneck and have been proven to play important roles in the treatment of esophageal cancer. The current research progress of the main targets and their related targeted drugs in molecular targeted therapy and immunotherapy for esophageal cancer were reviewed in this article, which provided reference for the application of precision medicine in the field of esophageal cancer.