Intervenções terapêuticas não farmacológicas para o tratamento de úlceras no pé diabético: revisão integrativa / Intervenciones terapéuticas no farmacológicas para el tratamiento de las úlceras diabéticas: revisión integral de la literatura / Non-pharmacological therapeutic interventions for the treatment of diabetic foot ulcers: an integrative literature review

Introdução: As úlceras no pé diabético surgem da interação complexa entreneuropatia periférica e doença arterial periférica, comprometendo a cicatrização após traumas. Objetivo: Explorar a diversidade de intervenções terapêuticas não farmacológicas que têm sido estudadas e avaliadas quanto à sua eficácia e segurança no tratamento de úlceras no pé diabético. Metodologia: Pesquisa do tipo revisão integrativa da literatura. Para obtenção dos resultados foi realizado um levantamento nas plataformas PubMed e Biblioteca Virtual em Saúde. Para elaboração dos resultados foram selecionados 21 artigos. Resultados: As intervenções encontradas foram oxigenoterapia hiperbárica, terapia de feridas por pressão negativa, uso de matriz dérmica, plasma rico em plaquetas, plasma atmosférico frio, tratamentos com curativos especiais e uso de solas rígidas, entre outros. Mostraram uma variabilidade na taxa de cicatrização e no tempo de fechamento da ferida, bem como na melhoria da regeneração tecidual. Conclusão: As pesquisas mostram uma diversidade de intervenções terapêuticas não farmacológicas utilizadas no tratamento de úlceras no pé diabético, ressaltando a necessidade de abordagens individualizadas e mais estudos para determinar a eficácia e segurança de cada intervenção (AU).

Introduction:Diabetic foot ulcers arise from the complex interaction between peripheral neuropathy and peripheral arterial disease, compromising wound healing after traumas. Objective:To explore the diversity of non-pharmacological therapeutic interventions that have been studied and evaluated for their effectiveness and safety in the treatment of diabetic foot ulcers. Methodology: An integrative literature review was conducted. The search for results was performed on the PubMed and Virtual Health Library platforms. Twenty-one articles were selected for result elaboration.Results:The identified interventions included hyperbaric oxygen therapy, negative pressure wound therapy, use of dermal matrix, platelet-rich plasma, cold atmospheric plasma, treatments with special dressings, and the use of rigid soles, among others. They exhibited variability in the healing rate and wound closure time, as well as improvement in tissue regeneration.Conclusion:The research demonstrates a diversity of non-pharmacological therapeutic interventions used in the treatment of diabetic foot ulcers, emphasizing the need for individualized approaches and further studies to determine the effectiveness and safety of each intervention (AU).

Introducción: Las úlceras en el pie diabético surgen de la interacción compleja entre neuropatía periférica y enfermedad arterial periférica, comprometiendo la cicatrización después de traumas.Objetivo: Explorar la diversidad de intervenciones terapéuticas no farmacológicas que han sido estudiadas y evaluadas en cuanto a su eficacia y seguridad en el tratamiento de úlceras en el pie diabético.Metodología: Investigación del tipo revisión integrativa de la literatura. Para obtener los resultados se realizó un estudio en las plataformas PubMed y Biblioteca Virtual en Salud. Para la elaboración de los resultados se seleccionaron 21 artículos. Resultados: Las intervenciones encontradas fueron oxigenoterapia hiperbárica, terapia de heridas por presión negativa, uso de matriz dérmica, plasma rico en plaquetas, plasma atmosférico frío, tratamientos con curativos especiales y uso de suelas rígidas, entre otros. Mostraron una variabilidad en la tasa de cicatrización y en el tiempo de cierre de la herida, así como en la mejora de la regeneración tisular. Conclusión: Las investigaciones muestran una diversidad de intervenciones terapéuticas no farmacológicas utilizadas en el tratamiento de úlceras en el pie diabético, resaltando la necesidad de enfoques individualizados y más estudios para determinar la eficacia y seguridad de cada intervención (AU).

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Práticas de autocuidado com os pés realizadas por homens com diabetes mellitus / Foot self-care practices performed by men with diabetes mellitus

Identificar o conhecimento e as formas de adesão as práticas de autocuidado com os pés por homens com diabetes mellitus. Método: Pesquisa do tipo exploratória, descritiva com abordagem qualitativa, realizada em duas unidades de atenção primária e uma unidade de atenção secundária do município de Fortaleza-CE. recebeu aprovação do Comitê de Ética em Pesquisa da UNIFOR de n. 5.100.589. Resultados: Dentro do universo de homens com diabetes foram entrevistados 26 homens na faixa etária de 45 a 81 anos, predominando-se aqueles com 48 a 69 de idade (84,6%), a escolaridade variou do analfabeto a ensino superior completo, sendo em sua maioria com fundamental incompleto (42,3%). Conclusão: Percebeu-se que os pacientes com maior nível de conhecimento apresentaram mais chances de praticar o autocuidado. Entretanto, notou-se que os déficits mesmo quando são isolados, podem oferecer o mesmo potencial de risco.(AU)

To identify the knowledge and forms of adherence to foot self-care practices by men with diabetes mellitus. Method: This is an exploratory, descriptive study with a qualitative approach, carried out in two primary care units and one secondary care unit in the city of Fortaleza-CE. The study received approval from the UNIFOR Research Ethics Committee (n. 5.100.589). Results: Within the universe of men with diabetes, 26 men aged between 45 and 81 were interviewed, with a predominance of those aged between 48 and 69 (84.6%). The level of education ranged from illiterate to complete higher education, with the majority having incomplete primary education (42.3%). Conclusion: Patients with a higher level of knowledge were more likely to practice self-care. However, it was noted that deficits, even when isolated, can offer the same risk potential.(AU)

Identificar el conocimiento y las formas de adherencia a las prácticas de autocuidado de los pies por hombres con diabetes mellitus. Método: Se trata de un estudio exploratorio, descriptivo, con abordaje cualitativo, realizado en dos unidades de atención primaria y una unidad de atención secundaria de la ciudad de Fortaleza, Ceará. El estudio recibió aprobación del Comité de Ética en Investigación de la UNIFOR (n. 5.100.589). Resultados: Dentro del universo de hombres con diabetes, fueron entrevistados 26 hombres con edades comprendidas entre 45 y 81 años, predominando los de edades comprendidas entre 48 y 69 años (84,6%), su nivel de escolaridad osciló entre analfabetos y estudios superiores completos, siendo la mayoría con estudios primarios incompletos (42,3%). Conclusión: Los pacientes con un mayor nivel de conocimientos eran más propensos a practicar el autocuidado. Sin embargo, se observó que los déficits, incluso aislados, pueden ofrecer el mismo potencial de riesgo.(AU)

Causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico Nacional - Hospital Nacional / Precipiting causes of acute hyperglycemic crisis in patients in the Centro Médico Nacional - Hospital Nacional

Introducción: las crisis hiperglicémicas agudas son las emergencias endocrinológicas más frecuentes en la práctica clínica y junto a la hipoglucemia se las describe como las complicaciones metabólicas agudas graves del paciente diabético. Objetivo: identificar las causas precipitantes de crisis hiperglicémicas agudas en pacientes internados en el Centro Médico - Hospital Nacional. Metodología: estudio observacional, descriptivo, de corte transversal de pacientes internados en el Centro Médico Hospital Nacional, durante el periodo de mayo 2021 a octubre del 2023. Los datos fueron obtenidos con la revisión de las fichas clínicas. Resultados: de los 100 pacientes evaluados, la crisis hiperglicémica aguda más frecuente fue la Cetoacidosis diabética (CAD) 53 %, seguida del Estado hiperosmolar hiperglicémico (EHH) 25 % y el estado mixto 22 %. Los desencadenantes más frecuentes fueron el abandono del tratamiento, debut de la enfermedad e infecciones. La mortalidad global fue del 12 %. Conclusión: la causa más frecuente de descompensación fueron el abandono del tratamiento, la diabetes de novo y procesos infecciosos.

Introduction: hyperglycemic crises are the most frequent endocrinological emergencies in clinical practice and, along with hypoglycemia, are described as serious acute metabolic complications in diabetic patients. Objective: to identify the precipiting causes of acute hyperglycemic crisis in hospitalized patients in the Centro Médico Nacional - Hospital National. Methodology: this was an observational, descriptive, cross -sectional study of patients hospitalized at the Centro Médico Nacional - Hospital National, from May 2021 to October 2023. The data were obtained from a review of the clinical records. Results: Of the 100 patients evaluated, the most frequent acute hyperglycemic crisis was diabetic ketoacidosis (CAD) 53 %, followed by the hyperglycemic hyperosmolar state (EHH) 25 % and the mixed state 22 %. The most frequent triggers were the abandonment of treatment, disease debut and infections. Global mortality was 12 %. Conclusion: the most frequent causes of decompensations were abandoning treatment, novo diabetes and infectious processes.

Complicaciones vasculares en pacientes diabéticos con hemoglobina glicosilada alterada internados en el Centro Médico Nacional - Hospital Nacional periodo 2022 - 2023 / Vascular complications in diabetic patients with altered glycated hemoglobin admitted to Centro Médico Nacional - Hospital Nacional period 2022 ­ 2023

Introducción: la diabetes mellitus es una enfermedad crónica que, al no ser controlada, puede desencadenar en complicaciones macro y microvasculares. Uno de los indicadores de un adecuado control glucémico es la hemoglobina glicosilada. Objetivos: determinar la frecuencia de complicaciones macro y microvasculares en pacientes diabéticos tipo 2 con hemoglobina glicosilada alterada internados en el Hospital Nacional de Itauguá periodo 2022 - 2023 Metodología: estudio observacional, descriptivo de corte transversal que incluyó a 170 pacientes adultos internados en el servicio de clínica médica del Hospital Nacional (Itauguá, Paraguay) durante los años 2022 y 2023. Resultados: la edad media fue de 58 ± 12 años, con predominio del sexo femenino (51 %). La complicación más frecuentemente diagnosticada fue la enfermedad del pie relacionada a la diabetes con 83 pacientes (49 %), seguido por retinopatía diabética 23 (14 %). El valor promedio de hemoglobina glicosilada fue de 10 ± 2 %. Solamente 6 (4 %) del total de pacientes presentó un valor de HbA1C≥ 7,1 %. La comorbilidad asociada más frecuente fue la hipertensión arterial 87 (51 %). El 91 % de los pacientes conocía ser portador de la enfermedad, el 80 % recibía algún tipo de tratamiento. Conclusiones: el pie diabético fue la complicación vascular diagnosticada con mayor ,frecuencia, especialmente en pacientes con HbA1C≥ 7,1 %.

Introduction: diabetes mellitus is a chronic disease that, if not controlled, can lead to macro- and microvascular complications. One of the indicators of adequate glycemic control is glycosylated hemoglobin. Objectives: to determine the frequency of macro and microvascular complications in type 2 diabetic patients with altered glycosylated hemoglobin admitted to the Hospital Nacional from 2022 to 2023 Methodology: this was an observational, descriptive, cross-sectional study that included 170 adult patients admitted to the Internal Medicine service of the Hospital Nacional (Itauguá, Paraguay) during the years 2022 and 2023. Results: the mean age was 58 ± 12 years, with a predominance of the female sex (51 %). The most frequently diagnosed complication was foot disease related to diabetes with 83 patients (49 %), followed by diabetic retinopathy 23 (14 %). The average value of glycosylated hemoglobin was 10 ± 2 %. Only 6 (4 %) of the total patients had an HbA1C value ≤7 %. The most frequent associated comorbidity was arterial hypertension 87 (51 %). 91 % of the patients knew they were carriers of the disease, 80 % received some type of treatment. Conclusions: diabetic foot was the most frequently diagnosed vascular complication, especially in patients with HbA1C ≥7.1 %.

Signaling Pathways Related to Renal Interstitial Fibrosis in Diabetic Kidney Disease Regulated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.

Exploring Modern Mechanism of Treating Diabetic Retinopathy and Coronary Heart Disease from Perspective of Blood Stasis Under Viewpoint of Treating Different Diseases with the Same Method / 中国实验方剂学杂志

Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.

Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L-1 glucose+10% blank serum）， model （30 mmol·L-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L-1 glucose+10% blank serum+1 μmol·L-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe2+ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe2+， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe2+， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism / 中国药房

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

Optical coherence tomography angiography manifestations of different degrees of nonproliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P&#x0026;#x003C;0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P&#x0026;#x003C;0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

Research progress of adipokines and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is one of the common microangiopathy in diabetes and the main cause of blindness in adults. It can be seen that it is very important to find the specific target of DR prevention and treatment. Adipose tissue is not only an energy storage tissue, but also an active endocrine organ, which can release a variety of cytokines, called adipokines. Studies have shown that adipokines play an important role in the occurrence and development of DR. Adipokines can not only directly act on vascular endothelium through blood circulation, but also indirectly affect vascular endothelial function by affecting the activity of sympathetic nervous system and insulin sensitivity, which leads to dysfunction of vascular endothelial cells, increased retinal vascular permeability, neurodegeneration and neovascularization, and finally leads to the destruction of blood-retinal barrier. In recent years, the role of some new adipokines in DR has been paid more and more attention. This paper reviews the related research of several new adipokines in DR.

Effect of Intestinal Microecology on Diabetic Kidney Disease Based on Yin-Yang Theory / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is the main cause of end-stage renal disease. Its high prevalence， mortality rate， and medical cost bring a heavy economic burden to society and families， and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body， which is involved in important life activities such as material and energy metabolism， immune system regulation， and signal transduction， thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken， intestinal microbiota imbalance， intestinal mucosal barrier damage， immune dysfunction， and reduction of metabolite short-chain fatty acids （SCFAs） will occur， which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine （TCM）， the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang， or Yin deficiency affecting Yang， or Yang deficiency affecting Yin， or waning and waxing of Yin and Yang. For different pathogenesis changes， "Yin disease treated through Yang"， "treating Yin for Yang"， or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota， inhibit immune inflammation， protect intestinal mucosal barrier， and increase SCFAs through TCM， thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory， this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.

Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Influencing factors of telangiectasia secondary to diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the influencing factors of abnormal telangiectasia secondary to diabetic retinopathy(DR).METHODS: Prospective studies. A total of 153 cases(240 eyes)with DR treated in our hospital from January 2021 to January 2023 were selected to analyze the risk factors of abnormal telangiectasia secondary to DR and its predictive efficacy.RESULTS: The patients were divided into dilated group(77 eyes of 40 cases)and non-dilated group(163 eyes of 113 cases)according to whether they had secondary abnormal telangiectasia. There were significant differences in diabetic macular edema, hard exudates grade and fasting blood glucose level between the two groups(P&#x0026;#x003C;0.05). Logistic regression analysis showed that diabetic macular edema, high hard exudates grade and high blood glucose level were the risk factors for abnormal telangiectasia secondary to DR(P&#x0026;#x003C;0.05).CONCLUSION: The occurrence of telangiectasia secondary to DR may be related to diabetic macular edema, grade 3 hard exudates and high blood glucose level.

Research progress on morphology of macular foveal avascular zone in ocular diseases based on optical coherence tomography angiography measurement / 国际眼科杂志(Guoji Yanke Zazhi)

The foveal avascular zone(FAZ)is the most sensitive region of the retina, which is interconnected by the macular capillary plexus. Its morphology can indirectly reflect the alterations of macular microcirculation. With strong repeatability and reliability, optical coherence tomography angiography(OCTA)can non-invasively visualize and quantify the FAZ. The great value of OCTA makes it an important supplemental examination tool in ophthalmology and other professions. The area and perimeter of FAZ have been demonstrated to be an effective clinical diagnostic indicator in high myopia, diabetic retinopathy, glaucoma and other ocular diseases. In recent years, the geometry of FAZ has also proven to have clinical value. The parameters describing the geometry of FAZ, such as circularity index, acircularity index and axial ratio, provide a new perspective for ocular disease research. The comprehensive investigation of the morphological characteristics of the FAZ is helpful to explore the pathological mechanism of the occurrence and development of ocular diseases, predict preclinical changes, make pathological stages of the disease precise, and provide a theoretical basis for monitoring the disease's progression and assessing patients' visual prognosis.

Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS: Diabetic mice models were established and they were gavaged by fenofibrate. H&#x0026;#x0026; E staining and transmission electron microscopy were used to observe the impairments of retinal neurons. Real-time PCR was used to examine the expression of miR-26a-5p, and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice. The expression level of nuclear factor-κB(NF-κB), interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS: When compared with the diabetic mice, fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer. While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice, with significant statistical significance(P&#x0026;#x003C;0.05).CONCLUSIONS: Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN, attenuating the inflammatory response and alleviating retinal cell injury.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P&#x0026;#x003C;0.001). Compared with the control group, the noDR group had significantly higher AVD(P&#x0026;#x003C;0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P&#x0026;#x003C;0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Treatment of Traditional Chinese Medicine for Diabetic Peripheral Neuropathy Based on Mitochondrial Quality Control： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.

Protective Effect of Total Lignans of Arctii Fructus on Retina in Rat Model of Type 2 Diabetes Mellitus / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of total lignans of Arctii Fructus on the retinal tissue in the rat model of type 2 diabetes mellitus. MethodWistar rats were randomized into normal， model， solvent， Shuangdan Mingmu Capsules （618 mg·kg-1）， and low-， medium-， and high-dose （100， 200， 400 mg·kg-1， respectively） total lignans of Arctii Fructus groups， with 16 rats in each group. The rat model was established by streptozotocin （STZ） combined with a high-fat diet and administrated with corresponding drugs by gavage once a day for 14 weeks. At the 14th week， blood was sampled for the collection of serum from the abdominal aorta after anesthesia， and bilateral eyeballs were collected and frozen. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of the retinal tissue in rats. The pathological changes of retinal vascular network in rats were observed by retinal vascular tissue digestion and mounting The levels of vascular endothelial growth factor （VEGF）， tumor necrosis factor-α （TNF-α）， and intercellular adhesion molecule-1 （ICAM-1） in the serum were determined by the ELISA kit. ResultCompared with the normal group， the solvent group showed pathological changes in the retinal tissue， reduced retinal ganglion cells （P<0.01）， and retinal thinning （P<0.01）， decreased E/P value in retinal blood vessels （P<0.01）， and elevated serum levels of VEGF， TNF-α， and ICAM-1 （P<0.01）. Compared with the model group， the total lignans of Arctii Fructus increased the retinal ganglion cells （P<0.01）， thickened the retina （P<0.01）， and lowered the serum levels of VEGF， TNF-α， and ICAM-1 （P<0.05， P<0.01）. ConclusionTotal lignans of Arctii Fructus may lower the VEGF， TNF-α， and ICAM-1 levels to protect the retina.