Níveis séricos de magnésio, sua associação com diabetes mellitus tipo 2 e suas complicações/comorbidades com enfâse na doença cardiovascular / Serum magnesium levels and their association with type 2 diabetes mellitus and its complications/comorbidites, especially cardiovascular disease / Niveles séricos de magnesio y su asociación con diabetes mellitus tipo 2, sus complicaciones/comorbilidades con énfasis en la enfermedad cardiovascular

O diabetes mellitus tipo 2 (DM2) é uma doença que apresenta mecanismos fisiopatológicos multifatoriais e complexos, tendo como base a resistência insulínica (RI) e como consequências as doenças cardiovasculares (DCV). A hipomagnesemia tem sido implicada tanto na RI como em complicações micro e macrovasculares, incluindo-se as DCV que são consideradas a causa mais importante de morbimortalidade no DM2. Neste contexto, o presente estudo visa avaliar níveis séricos de magnésio (Mg) em pacientes diabéticos e sua possível associação com complicações crônicas e comorbidades, tendo como ênfase as doenças cardiovasculares; e identificar possível valor do nível sérico a ser considerado em nossa população a fim de rever sua verdadeira aplicabilidade clínica. Trata-se de estudo transversal, descritivo e analítico, envolvendo 99 pacientes com DM2 de ambos os sexos, atendidos em ambulatório público na cidade de Salvador (BA). Utilizou-se como instrumentos de pesquisa questionário de dados sociodemográficos e antropométricos; recordatório alimentar de 24 horas e análise bioquímica do magnésio sérico. Também foram registradas comorbidades e complicações crônicas dos pacientes, tais como hipertensão arterial, doença arterial coronariana, doença arterial obstrutiva periférica, arritmia cardíaca, acidente vascular cerebral, dislipidemia, neuropatia sensitiva periférica, retinopatia e nefropatia diabéticas. Os dados foram expressos por tabelas de forma descritiva e analítica. Os indivíduos foram divididos em dois grupos, magnésio baixo e normal/alto, e suas variáveis foram comparadas por meio de testes de hipóteses. Nossos achados evidenciaram nível sérico médio de magnésio de 1,97 mg% (IC 1,69 a 2,25 mg%) no total da amostra. Entre aqueles com magnésio baixo, níveis subclínicos estavam presentes em 29 sujeitos (29,3%), e níveis de hipomagnesemia em 34 indivíduos (34,3%). O nível médio do Mg no total da amostra diferiu significativamente (p<0,001) do valor normal ideal, mas não diferiu do considerado subclínico (p 0,311). No grupo com hipomagnesemia houve predomínio do sexo feminino e de pacientes com maior escolaridade. Glicemia de jejum foi mais elevada no grupo Mg baixo, e hemoglobina glicada no grupo Mg normal/alto, mas ambos sem diferença estatística. Níveis baixos de vitamina B12 foram encontrados em 12 pacientes (12,1%) e os níveis mais baixos de magnésio estavam presentes nos pacientes com deficiência de vitamina B12 (1,81±0,24 versus 2,01±0,29) com p=0,027. Antidiabéticos orais foram mais utilizados no grupo com Mg baixo. Não houve diferença entre magnésio sérico, ingestão calórica e magnésio e cálcio alimentares. Pacientes com DCV tiveram média de 2,01 mg% (IC 1,69-2,33 mg%) para o Mg. A doença cardiovascular esteve presente em 47,5% da amostra e pacientes com esta morbidade apresentaram 29,8% de prevalência de hipomagnesemia; infarto agudo do miocárdio (IAM) foi mais frequente no grupo com Mg normal/alto. Nossos dados apontam que hipomagnesemia em pacientes diabéticos deve ser considerada em níveis clínicos e subclínicos. Níveis baixos de Mg também estiveram associados à vitamina B12 baixa. Pacientes que apresentaram doenças cardiovasculares associadas também tiveram importante prevalência de hipomagnesemia incluindo níveis subclínicos, com exceção nos casos de IAM, em que níveis do magnésio sérico mantiveram-se no intervalo considerado normal ideal evidenciado por significativa diferença estatística (p<0,005).

Diabetes mellitus type 2 (DM2) is a multifactorial disease with complex physiopathological mechanisms, in which insulin resistance (IR) and its consequences, such as cardiovascular diseases (CVD), form its basis. Hypomagnesemia has been implicated in IR and micro and macrovascular complications, including CVD, which is considered the most important cause of morbidity and mortality in DM2. This study aims to evaluate serum magnesium (Mg) levels in diabetic patients and its possible association with chronic complications and comorbidities (especially cardiovascular diseases) and to find a possible serum level value to be considered in its population to review its true clinical applicability. This cross-sectional, descriptive, and analytical study involved 99 DM2 patients of all sexes who were served in a public outpatient clinic in Salvador-Ba. A sociodemographic and anthropometric data questionnaire, a 24-hour food recall, and serum magnesium analysis were used as research instruments. The comorbidities and chronic complications of patients, such as hypertension, coronary artery disease, peripheral arterial obstructive disease, cardiac arrhythmia, cerebrovascular accident, dyslipidemia, peripheral sensory neuropathy, diabetic retinopathy, and nephropathy, were also recorded. The data were expressed in descriptive and analytical tables. The individuals were divided into two groups, low and normal/high magnesium, and their variables were compared using hypothesis tests. Our findings showed an average serum magnesium level of 1.97 mg% (IC 1.69 to 2.25 mg%) in the whole sample. In those with low magnesium, subclinical levels occurred in 29 subjects (29.3%)and hypomagnesemia, in 34 individuals (34.3%). The median Mg level in the total sample significantly differed (p<0.001) from the ideal normal value, but failed to do in relation to the subclinical value (p=0.311). The hypomagnesemia group showed a predominance of women and patients with higher education. Fasting glucose was higher in the low Mg group and glycated hemoglobin in the normal/high Mg group, both without statistical differences. Low levels of vitamin B12 occurred in 12 patients (12.1%) and the lowest magnesium levels, in patients with vitamin B12 deficiency (1.81±0.24 versus 2.01±0.29) (p=0.027). Oral antidiabetics were more used in the group with low Mg. Serum magnesium, caloric intake, and dietetic magnesium and calcium showed no differences. Patients with CVD had an Mg average of 2.01 mg% (IC 1.69-2.33 mg%). Cardiovascular disease occurred in 47.5% of the sample. Patients with this morbidity had a 29.8% prevalence of hypomagnesemia. Moreover, myocardial infarction occurred more often in the normal/high Mg group. Data suggest that hypomagnesemia in diabetic patients should be considered at clinical and subclinical levels. Low Mg levels were also associated with low vitamin B12. Patients who showed cardiovascular diseases also had a high prevalence of hypomagnesemia, including subclinical levels, except in cases of myocardial infarction, in which serum magnesium levels remained within the normal ideal range, as evinced by its significant statistical difference (p<0.005).

La diabetes mellitus tipo 2 (DM2) es una enfermedad con mecanismos fisiopatológicos multifactoriales y complejos caracterizada por la resistencia a la insulina (RI) y sus consecuencias, como las enfermedades cardiovasculares (ECV). La hipomagnesemia está asociada con la RI y las complicaciones micro y macrovasculares, incluyendo las ECV, que se consideran la principal causa de morbimortalidad por la DM2. En este contexto, este estudio tiene como objetivo evaluar los niveles séricos de magnesio (Mg) en pacientes diabéticos y la posible asociación con complicaciones crónicas y comorbilidades, con énfasis en las enfermedades cardiovasculares; e identificar un posible valor de nivel sérico para considerar en esta población con el fin de revisar su verdadera aplicabilidad clínica. Se trata de un estudio transversal, descriptivo y analítico, en el cual participaron 99 pacientes con DM2 de ambos sexos, atendidos en un centro ambulatorio público en la ciudad de Salvador (Bahía, Brasil). Se utilizaron un cuestionario de datos sociodemográficos y antropométricos, un recordatorio alimentario de 24 horas y un análisis bioquímico del magnesio sérico. También se registraron las comorbilidades y complicaciones crónicas de los pacientes, como hipertensión arterial, enfermedad arterial coronaria, enfermedad arterial obstructiva periférica, arritmia cardíaca, accidente cerebrovascular, dislipidemia, neuropatía sensorial periférica, retinopatía y nefropatía diabética. Los datos se dispusieron en tablas para su análisis y descripción. Los individuos se separaron en dos grupos: bajo magnesio y normal/alto magnesio, y se compararon sus variables mediante pruebas de hipótesis. Los hallazgos evidenciaron un nivel sérico medio de magnesio de 1,97 mg% (IC 1,69 a 2,25 mg%) en el total de la muestra. Los bajos niveles subclínicos de magnesio estaban presentes en 29 sujetos (29,3%), y la hipomagnesemia en 34 individuos (34,3%). El nivel medio de Mg en el total de la muestra tuvo una diferencia significativa (p<0,001) del valor normal ideal, pero no difirió del valor subclínico (p=0,311). En el grupo con hipomagnesemia hubo predominio del sexo femenino y de pacientes con mayor nivel de estudios. La glucemia en ayunas fue más alta en el grupo de bajo Mg, y la hemoglobina glucosilada en el grupo de normal/alto Mg, pero en ninguno de los dos se encontró diferencia estadística. Los bajos niveles de vitamina B12 se encontraron en 12 pacientes (12,1%), y los niveles más bajos de magnesio estaban presentes en los pacientes con deficiencia de vitamina B12 (1,81±0,24 versus 2,01±0,29) con p=0,027. Los antidiabéticos orales se utilizaron más en el grupo con bajo Mg. No hubo diferencia entre el magnesio sérico, la ingesta calórica, el magnesio y el calcio en la dieta. Los pacientes con ECV tuvieron una media de 2,01 mg% (IC 1,69-2,33 mg%) para Mg. La enfermedad cardiovascular estuvo presente en el 47,5% de la muestra, y los pacientes con esta morbilidad tuvieron una prevalencia del 29,8% de hipomagnesemia; el infarto agudo de miocardio (IAM) fue más frecuente en el grupo con normal/alto Mg. Los resultados demuestran que la hipomagnesemia en los pacientes diabéticos debe considerarse en los niveles clínicos y subclínicos. Los bajos niveles de Mg también estuvieron asociados a bajos niveles de vitamina B12. Los pacientes que presentaron enfermedades cardiovasculares asociadas también tuvieron una alta prevalencia de hipomagnesemia, incluidos los niveles subclínicos, con excepción de los casos de IAM en los que los niveles séricos de magnesio se mantuvieron dentro del intervalo considerado normal ideal, evidenciado por una diferencia estadísticamente significativa (p<0,005).

Albúmina en cirrosis: perspectiva inflamatoria / Albumin in cirrhosis: inflammatory perspective

La albúmina sérica humana es la proteína más abundante en el plasma, su estructura molecular le confiere estabilidad, pero también flexibilidad para ligar y transportar un amplio rango de moléculas. Su función oncótica es la propiedad más reconocida que la lleva a introducirse en la terapéutica médica como un expansor de volumen. Sin embargo, en los últimos años se le han adicionado funciones con carácter antioxidante, inmunomodulador y de estabilización endotelial, que hacen presumir que su impacto terapéutico está más allá de sus funciones volumétricas. En los últimos años, específicamente en la cirrosis y la falla hepática aguda sobre crónica, se ha tenido un cambio en el paradigma fisiológico, desde una perspectiva netamente hemodinámica hacia una perspectiva inflamatoria, en donde las funciones oncóticas y no oncóticas de la albúmina están alteradas y tienen un carácter pronóstico en estas entidades. Este conocimiento creciente, desde una perspectiva inflamatoria, hace que se fortalezca el uso terapéutico de la albúmina sérica humana desde las indicaciones tradicionales como prevención de la disfunción circulatoria posparacentesis, prevención y tratamiento de lesión renal aguda, hasta las discusiones para administración a largo plazo en pacientes cirróticos con ascitis.

Human serum albumin is the most abundant protein in plasma, with a molecular structure that provides stability while also allowing flexibility to bind and transport a wide range of molecules. Its oncotic function is the most recognized property, leading to its introduction in medical therapy as a volume expander. However, in recent years, additional functions with antioxidant, immunomodulatory, and endothelial stabilization properties have been identified, suggesting that its therapeutic impact extends beyond its volumetric functions. Specifically, in cirrhosis and acute-on-chronic liver failure, there has been a shift in the pathophysiological paradigm from a purely hemodynamic perspective to an inflammatory perspective, where both oncotic and non-oncotic functions of albumin are altered and have prognostic significance in these conditions. This growing understanding from an inflammatory perspective strengthens the therapeutic use of human serum albumin, not only for traditional indications such as the prevention of post-paracentesis circulatory disfunction, prevention and treatment of acute kidney injury, but also for discussions regarding long-term administration in cirrhotic patients with ascites.

Inhibition of triggering receptor expressed on myeloid cells-1(TREM-1)attenuates chronic intermittent hypoxia-induced atherosclerosis in mouse models / 基础医学与临床

Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Analysis of prognostic factors in patients with acute diquat poisoning / 中华急诊医学杂志

Objective:To investigate the factors influencing the short-term prognosis of patients with acute diquat poisoning (ADQP).Methods:Patients with ADQP admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Occupational Disease Prevention Hospital from August 2015 to July 2022 were retrospectively selected. Patients were divided into survival group and death group according to 30-day survival status after poisoning. The general data and the results of the first laboratory examination after admission were compared between the two groups. Logistic regression analysis was used to analyze the independent risk factors associated with prognosis. And the receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value of risk factors in patients with ADQP.Results:A total of 79 ADQP patients were included in this study, including 40 patients in the survival group and 39 patients in the death group. There were statistically significant differences in the age, poisoning dose, white blood cell, alanine aminotransferase, aspartate aminotransferase, serum creatinine, blood urea, neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and systemic immune inflammation index (SII) between survival and death groups (all P<0.05). Multivariate logistic regression analysis showed that the poisoning dose ( OR=1.018, 95% CI: 1.001-1.035, P=0.033), serum creatinine ( OR=1.049, 95% CI: 1.005-1.095, P=0.028), and SII ( OR=1.001, 95% CI: 1.000-1.002, P=0.029) were independent risk factors for the prognosis of patients with diquat poisoning. The areas under the curves of the combined detection of poisoning dose, serum creatinine and SII was 0.968, the sensitivity was 0.949, and the specificity was 0.900, which were higher than those of the single index. Conclusions:The poisoning dose, serum creatinine and SII are independent prognostic predictors of patients with ADQP. The combination of three independent factors has higher sensitivity and specificity in evaluating the prognosis of ADQP, which could be used as a reliable indicator to predict the prognosis of patients with ADQP.

Screening of early risk factors and prediction of prognosis in patients with diquat poisoning / 中华急诊医学杂志

Objective:To analyze the change characteristics of creatinine level in the early stage of patients with diquat (DQ) poisoning, and to explore the early risk factors and the value of prognosis.Methods:A retrospective analysis was carried out on patients with DQ admitted to the the first affiliated hospital of Zhengzhou University from January 2020 to June 2022. The DQ patients were divided into death group and the survival group according to the 28 days survival status after posioning. The basic data and serum indexes and blood gas analysis of the patients on day 1 (D1), day 3 (D3) and day 5 (D5) were collected. The difference of clinical features between the two groups was analyzed, the variables were screened by multiple logistic regression analysis, and the predictive value of the variables was evaluated by drawing receiver operating characteristic curve (ROC curve).Results:A total of 88 patients were included, including 40 patients in the survival group and 48 patients in the death group. The toxic dose in death group was significantly higher than that in survival group [100(40.00, 120.00) mL vs. 50.00(20.00, 90.00) mL, P=0.003]. The higher the toxic dose, the higher the fatality rate. All 4 patients with oral doses greater than 200 mL died. Compared with the survival group, the levels of alanine aminotransferase (ALT) (D3, D5), creatinine (CR) (D3, D5), blood amylase (AMY) (D5) and oxygen partial pressure (PaO 2) (D5) in the death group were significantly higher than those in the survival group (all P<0.05). Multiple Logistic regression analysis showed that CR (D3) and AMY(D5) were independent risk factors for death after poisoning, and PaO 2(D5) was independent protective factor. ROC curve showed that the areas under ROC curve of CR (D3), AMY (D5) and PaO 2 (D5) were 0.814, 0.741 and 0.702, respectively. Conclusion:The higher the oral dose, the higher the death rate. After admission, CR(D3), AMY (D5) and PaO 2 (D5) were independent factors influencing the prognosis of DQ poisoning. In particular, CR (D3) is more effective in predicting death after poisoning.

Diagnostic value of serum miR-141 in colorectal cancer and changes of serum miR-141 level after radical resection / 临床外科杂志

Objective To investigate the potential value of miR-141 as a diagnostic blood biomarker expression level in patients with colorectal cancer(CRC)and its change after radical CRC resection.Methods 75 CRC patients admitted to Affiliated to Medical College of Xi'an Jiaotong University 3201 Hospital from April 2019 to March 2021 were included in the experimental group,and 20 patients who received planned surgery for inguinal hernia during the same period were used as non-cancer control group.Surgical tissue and serum samples of these patients were collected.Microarray analysis was performed for miRNAs with significant expression differences in CRC tissues and serum.Real-time quantitative PCR(qRT-PCR)was used to verify the expression level of miR-141 in serum samples of the patients before surgery and at the 3rd day after surgery,and the relationship between miR-141 and clinicopathological characteristics of CRC patients was analyzed.Results By miRNA microarray analysis,we confirmed that 12 miRNAs were up-regulated simultaneously in tissue and serum samples of CRC patients,among which miR-141 was the most significantly up-regulated.Meanwhile,the relative expression level of miR-141 in serum of CRC group was significantly higher than that of non-cancer control group after qRT-PCR verification[2.50(1.06,3.12)vs.0.97(0.68,1.21),Z=-5.842,P＜0.05].According to ROC curve analysis,the AUC value of preoperative serum miR-141 for the diagnosis of CRC was 0.927(95％CI:0.862～0.992).When serum miR-141 ≥ 1.418,the accuracy of distinguishing between CRC and non-cancer control groups was 90.53％.Combined detection of serum miR-141 could increase the diagnostic AUC value of carcinoembryonic antigen and carbohydrate antigen-199 to 0.944(95％CI:0.899-0.998).For CRC patients,the relative expression level of serum miR-141 after radical resection was significantly lower than that before surgery[1.85(1.29,2.22)vs.2.55(2.07,3.18),Z=-5.416,P＜0.001].For those who did not receive radical resection,the relative expression level of serum miR-141 after surgery was slightly lower than that before surgery[2.28(1.72,2.74)vs.2.45(2.06,2.85)],but the difference was not statistically significant(Z=-1.917,P=0.055).The expression level of Mir-141 in serum of CRC patients was correlated with UICC stage and histological grade(P＜0.05).Conclusion Serum miR-141 reflects the pathological changes of CRC patients and can be used as a biomarker for non-invasive diagnosis of CRC.

Predictive Value of Serum C18∶1-Cer and LPC18∶0 Levels in Early Pregnancy Women for Gestational Diabetes Mellitus / 现代检验医学杂志

Objective To explore the value of serum stearoyl sphingosine(C18∶1-Cer)and 1-stearoyl-sn-glycero-3-phospho-choline(LPC 18∶0)levels in pregnant women's serum samples during pregnancy in predicting gestational diabetes mellitus(GDM).Methods The clinical data and laboratory indicators of 126 pregnant women were retrospectively analyzed.The sub-jects were divided into GDM group(n=66)and control group(n=60)according to the GDM diagnosis results.Mass spec-trometry was used to detect the serum C18∶1-Cer and LPC18∶0 levels of the subjects in early and mid pregnancy.Logistic re-gression analysis was used to screen out the risk factors for GDM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of C18∶1-Cer,LPC18∶0 and their combination for GDM.Results Compared with the control group,the serum C18∶1-Cer and LPC18∶0 levels of the subjects in the GDM group were significantly increased in early(18.92±2.77ng/ml vs 23.47±4.18ng/ml,41.32±17.55ng/ml vs 88.08±16.02ng/ml)and mid pregnancy(23.14±4.10ng/ml vs 18.76±4.05ng/ml,84.60±14.53ng/ml vs 40.50±17.79ng/ml),and the differences were statistically significant(t=7.127,15.637;-5.984,2.174,all P＜0.05)C18∶1-Cer was positively correlated with fasting plasma glucose(FPG),fasting plasma insulin(FPI),homeostasis model assessment of insulin resistance(HOMA-IR),glycated hemoglobin(HbA1c)and triglyceride(TG)(r=0.458,0.209,0.317,0.223,0.219,all P<0.05).LPC18.0 was positively correlated with FPG,FPI,HOMA-IR,HbA1c,total cholesterol(TC)and TG(r= 0.715,0.426,0.580,0.465,0.232,0.372,all P<0.05).Logistic regression analysis results showed that C18∶1-Cer[OR(95%CI):1.522(1.136～2.039),P<0.05]and LPC18:0[OR(95%CI):1.198(1.102～1.302),P<0.001]were independent risk factors for GDM.ROC curve analysis results showed that the area under the curve(AUC)of serum C18∶1-Cer,LPC18∶0 and the combination of the two indicators were 0.819,0.971 and 0.986,respectively.The predictive performance of the combination of the two indicators was better than that of the single detection.Conclusion Serum C18∶1-Cer and LPC18∶0 in early pregnancy were closely related to the occurrence of GDM.C18∶1-Cer combined with LPC 18∶0 has a certain predictive value for the early diagnosis of GDM.

Research on Serum 25-Hydroxy Vitamin D Level in Healthy Children Aged 0～12 Years for Physical Examination in Xi'an Area / 现代检验医学杂志

Objective To investigate and evaluate the nutrition status in serum 25-hydroxy vitamin D[25(OH)D]levels of 0～12 years old children in Xi'an.Methods A total of 2 670 patients aged 0～12 years old who underwent routine physical examinations in Children's Health Department of the Second Hospital of Air Force Medical University were selected from March 2020 to July 2023,and the 25(OH)D data of these patients were conducted in retrospective analysis.The nutritional status of vitamin D in these children of different genders,ages and seasons were also analyzed.Results ①This study included 2 670 children aged 0～12 years old in Xi'an,with the average level of serum 25(OH)D was 40.80±18.00 ng/ml.Among them,38 cases(1.42%)had serum 25(OH)D deficiency,333 cases(12.47%)had serum 25(OH)D insufficience,and 2 299 cases(86.11%)had sufficient serum 25(OH)D.②There was a statistically significant difference in serum 25(OH)D levels among different age groups(H=1 524.23,P=0.000).The group aged 1～<4 has the highest value of 52.51±13.57 ng/ml,while the group aged 8～12 has the lowest value of 21.65±6.75 ng/ml.③The levels of serum 25(OH)D in summer(39.44±17.46 ng/ml)were lower than those in spring(41.96±17.76 ng/ml)and autumn(42.71±18.15 ng/ml),with statistical significant differences(Z=101.57,-134.06,all P<0.01).However,the deficiency and inadequate rate of serum 25(OH)D in winter(18.95%)was higher than those in spring,summer and autumn(13.52%,12.75%,12.36%),with statistical significant differences(χ2=14.32,P=0.026).④There was no statistically significant difference in serum 25(OH)D levels between genders(H=0.933,P=0.351).However,the deficiency and inadequate rate of serum 25(OH)D in boys(12.51%)was lower than that in girls(15.46%),and the difference was statistically significant(χ2=9.257,P=0.010).Conclusion The nutritional status of serum 25(OH)D in children aged 0～12 years in Xi'an area is comparatively fine,and it is necessary to strengthen the intake and supplementation of vitamin D in over 3 years old children.

Mechanism underlying the effect of Liuwei Dihuang Pill on osteolysis and osteogenesis induced by titanium particles / 中国组织工程研究

BACKGROUND:At present,a large number of studies have found that Liuwei Dihuang Pill can be used to treat osteoporosis,but there are few related studies on the differentiation and mineralization of osteoblasts induced by wear particles using Liuwei Dihuang Pill. OBJECTIVE:To investigate the positive effect of different concentrations of Liuwei Dihuang Pill-containing serum on titanium particle-induced mouse MC3T3-E1 osteoblast in vitro osteolysis model. METHODS:Drug-containing serum was extracted after oral administration of Liuwei Dihuang Pill.The best concentration of Liuwei Dihuang Pill-containing serum and titanium particles on the viability of MC3T3-E1 cells was screened.MC3T3-E1 cells were divided into three groups.The blank group was given osteoblastic differentiation culture.The model group was given titanium particles(5 μg/mL)ossification culture.The drug-containing serum group was given titanium particles(5 μg/mL)+ Liuwei Dihuang Pill-containing serum(10%,15%and 20%doses).Osteoblast viability was detected by CCK-8 assay.Cell alkaline phosphatase activity was detected by alkaline phosphatase staining.Cell mineralization was detected by silver nitrate(Von Kossa)and alizarin red staining.Expression levels of bone differentiation-related genes Runx-2,Osterix,Ocn,Axin,Alp,and Opn were detected by qRT-PCR.Wnt/β-catenin signaling pathways β-catenin,p-GSK-3β,GSK-3β,Runx2 and Osterix protein expression levels were detected by western blot assay. RESULTS AND CONCLUSION:(1)Liuwei Dihuang Pill-containing serum culture reversed the decrease in alkaline phosphatase activity of MC3T3E-1 cells induced by titanium particles,increased the alizarin red staining and calcification of MC3T3E-1 cells,increased the expression of osteogenesis-related genes in MC3T3E-1 cells,and increased the expression of proteins related to the Wnt/β-catenin signaling pathway.(2)These findings indicate that Liuwei Dihuang Pill-containing serum can reverse the inhibitory effect of titanium particles on the differentiation and mineralization of osteoblasts,upregulate the expression of osteogenesis-related genes,and its mechanism is related to the regulation of Wnt/β-catenin signaling pathway,suggesting that Liuwei Dihuang Pill is expected to become an effective drug for preventing aseptic loosening of artificial joints.

Analysis of serum differential proteomics in patients with acute cervical spondylotic radiculopathy / 中国组织工程研究

BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P＜0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.

Inhibitory effect of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438 on osteosarcoma / 中国组织工程研究

BACKGROUND:The most prominent transcription factor activated by tumor stem cells in osteosarcoma is EZH2,and silencing of EZH2 has been reported to inhibit osteosarcoma cell growth.Studies have confirmed that bovine serum albumin-chitosan nanoparticles are a drug delivery vector with excellent biocompatibility and biodegradability,and the albumin carrier can provide tumor-targeted drug delivery function. OBJECTIVE:To investigate the effect and mechanism of bovine serum albumin-chitosan nanoparticles loaded with EPZ6438(EZH2 inhibitor)for the treatment of osteosarcoma. METHODS:(1)Bovine serum albumin-chitosan nanoparticles loaded with and without EPZ6438 were prepared.The drug encapsulation rate and drug release rate of serum albumin-chitosan nanoparticles loaded with EPZ6438 were detected.(2)MG-63 cells were divided into four groups and added with PBS(control group),serum albumin-chitosan nanoparticle extract solution(blank nanoparticle group),EPZ6438 solution(free drug group),and serum albumin-chitosan nanoparticle extract loaded with EPZ6438(drug-loaded nanoparticle group),respectively.After 3 days of culture,cell apoptosis was detected by flow cytometry and the expression of caspase-3 mRNA was detected by RT-PCR.(3)Twelve nude mice were selected and the subcutaneous tumor-bearing mouse model was established by injecting MG-63 cell suspension under the armpit.After successful modeling,the mice were randomly divided into four groups for intervention.Normal saline(control group),serum albumin-chitosan nanoparticle solution(blank nanoparticle group),EPZ6438 solution(free drug group)and serum albumin-chitosan nanoparticle solution loaded with EPZ6438(drug-loaded nanoparticle group)were injected into tumor tissues,with three animals in each group.After 7 days of injection,the tumor volume and frozen sections of tumor tissue were observed by TUNEL staining. RESULTS AND CONCLUSION:(1)The drug encapsulation rate of the nanoparticles was about 8.8%,and the nanoparticles had a good drug release effect in pure water.The drug release amount was(34.72±1.93)μg at 24 hours,(48.58±1.10)μg at 72 hours,(49.18±1.24)μg at 120 hours,and(50.25±1.13)μg at 168 hours.The drug release reached the plateau at 120 hours,and the release rate was about 97.9%.(2)After 3 days of cell culture with MG-63,the apoptotic rate in the control group and blank nanoparticle group was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.001),and the expression of caspase 3 mRNA was lower than that in the free drug group and drug-loaded nanoparticle group(P<0.000 1).(3)After 7 days of injection,the tumor volume of nude mice in the drug-loaded nanoparticle group was smaller than that in the other three groups(P<0.05),and the percentage of TUNEL-positive cells in tumor tissue was higher than that in the other three groups(P<0.000 1).(4)The results verify that serum albumin-chitosan nanoparticles loaded with EPZ6438 can inhibit the growth of osteosarcoma by inducing apoptosis of tumor cells.

Serum differential proteomics between developmental cervical spinal stenosis and cervical spondylotic myelopathy / 中国组织工程研究

BACKGROUND:Previous studies have found that qi deficiency and blood stasis syndrome is the main syndrome among various TCM syndromes of cervical spondylotic myelopathy.However,there is no report on proteomic markers as early diagnosis indicators for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome to cervical spondylotic myelopathy. OBJECTIVE:To explore serum proteomics difference between developmental cervical spinal stenosis and cervical spondylotic myelopathy and to find and identify the potential serum biomarkers between them. METHODS:Serum samples of nine patients with cervical spondylotic myelopathy of qi deficiency and blood stasis syndrome(experimental group)and nine patients with developmental cervical spinal stenosis of qi deficiency and blood stasis syndrome(control group)were collected.The proteomic analysis was carried out by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry,so as to find and identify differentially expressed proteins. RESULTS AND CONCLUSION:A total of 1027 significantly differential proteins were initially screened by TMT technology and 89 significantly differential proteins were finally identified(P<0.05).Compared with the control group,there were 45 up-regulated proteins in the experimental group,such as α-actinin-4,α-actinin-1,cell division control protein 42 homolog,integrin-linked protein kinase and B-actin.Conversely,there were 44 down-regulated proteins in the experimental group compared with the control group,such as fibronectin,fibrinogen γ chain,fibrinogen α chain,fibrinogen β chain.Gene ontology enrichment analysis indicated that these differential proteins were involved in signal receptor binding,kinase binding,protein kinase activity,integrin binding,actin filament binding and other molecular functions.Based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis,20 common differential signal/metabolic pathways were identified,including Rap1 signaling pathway,adherens junction,tight junction,platelet activation,and regulation of actin cytoskeleton.Protein-protein interaction analysis showed that ILK,FGA,FGB,FGG,FN1,Cdc42,ACTN1,ACTN4 and ACTB were located at the nodes of protein-protein interaction network and were closely related to bone formation and destruction system,nervous system,coagulation system,cellular inflammation and other systems.To conclude,the serum differentially expressed proteins between developmental cervical spinal stenosis and cervical spondylotic myelopathy can be successfully screened by Tandem Mass Tag combined with liquid chromatography tandem mass spectrometry.ILK,FN1,CDC42 and ACTN 4 are identified as specific markers for the transformation of developmental cervical spinal stenosis with qi deficiency and blood stasis syndrome into cervical spondylotic myelopathy.These findings provide a basis for further clarifying the transformation mechanism.

Shexiang Huangqi compound dripping pills-containing serum promotes proliferation and differentiation of bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Bone marrow mesenchymal stem cells have been widely used to treat neurological diseases.However,due to limitations of the blood-brain barrier,low survival rate and differentiation rate of stem cells at damaged sites,the therapeutic effect is limited. OBJECTIVE:To investigate the effects of Shexiang Huangqi compound dripping pills on proliferation,migration and astrocyte differentiation of bone marrow mesenchymal stem cells. METHODS:Male SD rats were treated with Shexiang Huangqi compound dripping pills for 5 days after continuous gavage.Blood was collected from the abdominal aorta and serum was separated for later use.The effect of 5%,10%and 20%drug-containing serum on the proliferation of bone marrow mesenchymal stem cells was detected by CCK-8 assay.The effect of 10%drug-containing serum on lateral migration of bone marrow mesenchymal stem cells was observed by scratch test.Bone marrow mesenchymal stem cells were cultured in Transwell cells.The effects of 10%drug-containing serum on longitudinal migration of bone marrow mesenchymal stem cells were observed by crystal violet staining and DAPI nuclear staining.Differentiation of bone marrow mesenchymal stem cells into astrocytes was observed by inducing solution with 10%drug-containing serum or co-culture with astrocytes. RESULTS AND CONCLUSION:(1)10%and 20%drug-containing serum promoted cell proliferation more significantly on days 2 and 3,and there was no statistical difference between the two concentrations.(2)At 30 and 48 hours,bone marrow mesenchymal stem cell migration in 10%drug-containing serum group was significantly higher than that in the control group.(3)The number of bone marrow mesenchymal stem cells filtered through Transwell cells in 10%drug-containing serum group was higher than that in the control group.(4)10%drug-containing serum might promote the differentiation of bone marrow mesenchymal stem cells to astrocytes,but the differentiation effect was weak,and astrocytes might further promote the differentiation of bone marrow mesenchymal stem cells into astrocytes induced by drug-containing serum.(5)The results exhibited that the 10%drug-containing serum could promote the proliferation and migration of bone marrow mesenchymal stem cells in vitro.Co-culture with astrocytes may promote the differentiation of bone marrow mesenchymal stem cells towards astrocytes.

Targeted induction of human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum into neural stem cells / 中国组织工程研究

BACKGROUND:There are many kinds of cell media with different components,which have a great influence on cell growth.Several studies in and outside China have used serum-free media containing fetal bovine serum for in vitro amplification culture,but the use of media containing human peripheral blood serum to directionally induce human umbilical cord mesenchymal stem cells to neural stem cells and human peripheral blood serum to promote neural stem cells to differentiate into other nerve cells,so far there are few relevant studies. OBJECTIVE:To observe the feasibility of inducing human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum into neural stem cells. METHODS:(1)Human umbilical cord mesenchymal stem cells were cultured in DMEM/F-12 culture medium containing 10%human peripheral blood serum by volume fraction.Flow cytometry analysis was performed at the third passage to identify surface markers and alizarin red staining was used to detect osteogenic differentiation function.(2)The third-generation human umbilical cord mesenchymal stem cells were induced into neural stem cells using DMEM/F-12 medium containing 0.5%N2,1.5%B27,20 ng/mL basic fibroblast growth factor,and 20 ng/mL epidermal growth factor,and their surface markers were identified.(3)Well-growing human umbilical cord mesenchymal stem cell-derived neural stem cells were taken to prepare a single cell suspension.They were evenly inoculated into 96-well plates and incubated with DMEM/F-12 culture medium containing 10%human peripheral blood serum for 8 days.Then,hematoxylin-eosin staining,microtubule-associated protein 2,and glial fibrillary acidic protein immunofluorescence staining were performed to detect the differentiation of neural stem cells into other neural cells. RESULTS AND CONCLUSION:(1)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum grew in a spiral-like pattern and were distributed in multiple layers,with directional arrangement.The surface of human umbilical cord mesenchymal stem cells highly expressed CD44,CD105,CD29,and CD73.Cells stained with alizarin red showed a color reaction.(2)Human umbilical cord mesenchymal stem cells cultured with human peripheral blood serum could be induced to differentiate into neural stem cells,and the surface of neural stem cells was highly expressed with CD44,CD105,CD29,CD73,Nestin,NF-L,and GALC.(3)On day 8 of induced differentiation of neural stem cells,after staining with hematoxylin and eosin,it was found that the protruding protrusions were longer,with more branches and adjacent cells connected,presenting typical neural cell morphology.Immunofluorescence staining for microtubule-associated protein 2 and glial fibrillary acidic protein was positive.It is concluded that human umbilical cord mesenchymal stem cells cultured by human peripheral blood serum can be directly induced to differentiate into neural stem cells.Under the action of human peripheral blood serum,neural stem cells can differentiate into other neural cells as the culture time prolongs.

Serum differential proteomic analysis of developmental cervical canal stenosis / 中国组织工程研究

BACKGROUND:Serum-specific biomarkers between normal healthy individuals and populations with developmental cervical canal stenosis(Qi deficiency and blood stasis syndrome)have not been fully defined. OBJECTIVE:To screen and identify the potential biomarkers of developmental cervical canal stenosis with Qi deficiency and blood stasis. METHODS:Serum samples were collected from nine patients with developmental cervical canal stenosis with Qi deficiency and blood stasis and eight healthy people.Differentially expressed proteins in serum were screened and identified using isotope relative labeling and absolute quantification combined with liquid chromatography tandem mass spectrometry.Western blot was used to verify some significant differentially expressed proteins. RESULTS AND CONCLUSION:A total of 61 differentially expressed proteins(P<0.05)were identified using tandem mass spectrometry techniques.Compared with the healthy normal population group,14 differentially expressed proteins such as complement component C1q receptor,apolipoprotein A4,and C-C motif chemokine ligand 18 were significantly upregulated,while 47 differentially expressed proteins such as myosin light chain 3,mitochondrial translation elongation factor,and nucleolar phosphoprotein 1 were significantly downregulated.The results of gene ontology enrichment analysis indicated that these differentially expressed proteins might participate in molecular functions such as regulation of chromosomal tissue,mitochondrial membrane tissue,and muscle system processes.Protein-protein interaction network analysis showed that 38 common differential proteins,including complement component C1q receptor,apolipoprotein A4,C-C motif chemokine ligand 18,myosin light chain 3,mitochondrial translation elongation factor,and nucleolar phosphoprotein 1,were located at functional network nodes between healthy normal individuals and those with developmental cervical canal stenosis(Qi deficiency and blood stasis syndrome),and were closely related to the local energy metabolism of the cervical spine,the production of cervical vertebral osteocytes,and the formation of osteoclasts.The main differentially expressed protein myosin light chain 3 was validated using western blot assay,and the validation results were consistent with the proteomic results.To conclude,the preliminary discovery of differentially expressed proteins in serum between healthy normal individuals and those with developmental cervical canal stenosis(Qi deficiency and blood stasis syndrome)through absolute quantitative technology combined with liquid chromatography tandem mass spectrometry technology suggests that myosin light chain 3 may be a specific serum marker for developmental cervical canal stenosis(Qi deficiency and blood stasis syndrome).

A multi-model study of serum uric acid/albumin ratio in predicting acute kidney injury after PCI in STEMI patients / 现代医院

Objective To explore the potential of serum uric acid/albumin ratio(sUAR)as a predictive model for acute kidney injury(AKI)after PCI in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 166 STEMI patients admitted to Duchang Hospital from July 2021 to July 2023 were retrospectively selected and divided into two groups:the occurrence group(n =34)and the non-occurrence group(n =132)based on whether AKI occurred after PCI.Base-line data,biochemical indexes,and sUAR were compared between the two groups.Univariate and multivariate logistic regression were utilized to analyze the risk factors for AKI following PCI,and a nomogram prediction model was developed.The ROC curve was developed to analyze the predictive efficiency of the model.Results There were significant differences in age,hypertension,Killip classification,NLR,sUAR,LVEF,contrast agent dose,PCI operation time,and multi-vessel lesions between the two groups(P＜0.05).Older age(OR=1.066),Killip grade≥2(OR=7.174),elevated NLR(OR=4.440),increased sUAR(OR=2.071),high contrast agent dose(OR=1.104),and prolonged PCI operation duration(OR=1.044)were identified as the independent risk factors for AKI following PCI(P＜0.05).The AUC values for the NLR,sUAR,"NLR+sUAR"and no-mogram prediction models were 0.807(95%CI:0.717～0.897),0.810(95%CI:0.729～0.892),0.877(95%CI:0.808～0.946),0.940(95%CI:0.901～0.979),respectively.Bootstrap(B =1 000)internal validation indicated that the bias-corrected prediction curve was closely aligned with the ideal line,and the nomogram risk prediction model had good predictive a-bility.The decision-making curve analysis revealed that the model's threshold probability ranged from 0.01 to 0.90 with a net re-turn more than 0.Conclusion AKI after PCI in STEMI patients are closely related to such indicators as age,Killip classifica-tion,NLR,sUAR,contrast agent dose,and PCI operation duration.The nomogram prediction model demonstrates higher predic-tive efficiency for AKI after PCI compared to the single model and it holds better clinical application value.

Influencing factors and prediction model construction of diffuse chorioretinal atrophy in patients with high myopia / 眼科新进展

Objective To investigate the factors that lead to diffuse chorioretinal atrophy(DCA)in patients with high myopia(HM)and to establish a prediction model.Methods In this retrospective case-control study,a total of 169 HM patients(338 eyes)admitted to the Department of Ophthalmology,Harbin 242 Hospital from October 2018 to October 2022 were selected.All patients underwent comprehensive ophthalmic examination at the time of inclusion.The incidence of DCA was evaluated according to the International Photographic Classification and Grading System for myopic maculopa-thy,and the risk factors of DCA in HM patients were analyzed by multivariate Logistic regression.The predictive model of DCA in HM patients was established by the receiver operating characteristic curve(ROC)based on risk factors,and the calibration degree of the predictive model was tested by Hosmer-Lemeshow(H-L).Results Among the 169 patients,34 patients were divided into the DCA group,and 135 patients were divided into the non-DCA group;there were statistically significant differences in age and gender distribution between the two groups(both P＜0.05).The axial length(AL),pat-tern standard deviation(PSD),positive rate of carbonic anhydrase 2(CAII)antibody in the DCA group were higher than those in the non-DCA group,while the best corrected visual acuity(BCVA),mean defect(MD)of the visual field,spheri-cal equivalent(SE),deep retinal microvessel density(MVD)and serum 25-hydroxyvitamin D[25(OH)D]were lower than those in the non-DCA group(all P＜0.05).Older age,longer AL and positive CAII antibody were the risk factors for DCA in HM patients(all P＜0.05),while greater deep retinal MVD and higher 25(OH)D were the protective factors(both P＜0.05).ROC analysis showed that the area under the curve of the prediction model for DCA in HM patients was 0.864(95％CI:0.802-0.911,P＜0.001),and the sensitivity and specificity were 85.29％and 88.15％,respectively.According to the H-L test,the prediction model for DCA in HM patients was relatively consistent with the actual results(P＞0.05).Con-clusion The occurrence of DCA in HM patients is affected by age,AL,CAII antibody,deep retinal MVD and 25(OH)D level,and a prediction model established based on the above factors can predict the risk of DCA well.

Analysis of the interaction of fasting blood glucose and serum uric acid on di-abetic retinopathy / 眼科新进展

Objective To investigate the impact of the interaction of fasting blood glucose(FBG)and serum uric acid(SUA)on diabetic retinopathy(DR).Methods A total of 306 diabetes mellitus(DM)patients diagnosed and re-ceived comprehensive ophthalmic examination in the First Affiliated Hospital of Gannan Medical University from January 2019 to January 2021 were selected.According to the presence or absence of DR,these patients were divided into the DR group(178 patients)and the non-DR(NDR)group(128 patients).The general clinical data of patients in the two groups were compared.The least absolute shrinkage and selection operator(LASSO)regression method and multivariate Logistic regression analysis were used to screen the independent influencing factors of DR in DM patients,and the odds ratio of risk factors was calculated.The sensitivity analysis of the results was performed using the E-value method.The interaction of FBG and SUA on DR in DM patients was analyzed by an additive interaction model.The Nomogram model to predict DR in DM patients was constructed and verified internally.The receiver operating characteristic curve(ROC)was used to evalu-ate the effects of FBG,SUA and both FBG and SUA on DR in DM patients.Results Compared with the NDR group,the course of DM in the DR group was significantly longer,the proportion of patients with history of oral medication was signif-icantly lower,the proportion of patients with history of insulin therapy was significantly higher,and the levels of total cho-lesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,SUA and FBG were significantly higher(all P＜0.05).The history of insulin therapy,course of DM≥9.66 years,TG≥2.07 mmol·L-1,SUA ≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 were the risk factors for DR in DM pa-tients,while the history of oral medication was the protective factor for DR in DM patients.The Nomogram model based on the above independent risk factors was accurate in predicting the occurrence of DR in DM patients.SUA and FBG had inter-active effects on DR in DM patients.The value of SUA-FBG interaction in the diagnosis of DR was greater than that of both alone.Conclusion SUA≥ 297.73 μmol·L-1 and FBG ≥8.92 mmol·L-1 are the risk factors for DR in DM patients.The value of interaction of FBG and SUA in the diagnosis of DM accompanied by DR is greater than that of both alone.

Evaluation of the therapeutic effect of autologous serum on neurotrophic keratopathy with persistent corneal epithelial defect / 中华实验眼科杂志

Objective:To evaluate the outcomes of autologous serum eye drops on persistent corneal epithelial defect caused by neurotrophic keratopathy (NK).Methods:An observational case series study was performed.Twenty patients (20 eyes) diagnosed with NK and persistent corneal epithelial defect were enrolled in Beijing Tongren Hospital from January 2020 to January 2021.The affected eyes were graded according to the severity of the lesion and received individualized comprehensive treatment with domestic autologous serum eye drops as the main therapy.The healing time of the corneal epithelial defect after treatment was recorded.The diameter and area of the defect were marked by corneal fluorescein staining.Changes in the diameter and area of the defect before treatment and at 1, 2, 3, 4 and 8 weeks after treatment were observed by slit lamp microscopy at 10×.Logarithm of the minimum angle of resolution (LogMAR) visual acuity was recorded with a standard logarithmic visual chart before treatment and at 1, 2, 4, 12, and 24 weeks after treatment.Changes in corneal nerve fiber distribution and silk length of corneal perception were assessed by confocal laser scanning microscopy and Cochet-Bonnet esthesiometry, respectively, before treatment and at 4, 12, and 24 weeks after treatment.Influences of corneal defect characteristics on the healing time were analyzed by multiple linear regression analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital Affiliated to Capital Medical University (No.TRECKY2021-110). Written informed consent was obtained from each subject.Results:The corneal epithelial defect was 5.00 (4.00, 5.75) mm in diameter and 15.50 (12.00, 20.00) mm 2 in area before treatment.There were 45% (9/20) with corneal stroma edema and 35% (7/20) with endothelial fold.One diabetic patient with uveitis had a corneal epithelial defect area greater than 8 mm×6 mm and accepted additional corneal clearance and amniotic membrane transplantation after 2 weeks of autologous serum eye drops application.The other 19 patients received autologous serum eye drops therapy.All eyes showed complete recovery.The pretreatment duration of autologous serum eye drops ranged from 2 weeks to 3 months, with a mean of (39.55±25.34) days.The repair time of corneal epithelium ranged from 12 to 42 days, with a mean of (19.68±9.25) days.There were statistically significant differences in corneal defect diameter and area between before and after treatment ( χ2=43.130, 28.265; both at P<0.001). Corneal defect area and diameter decreased at various time points after treatment compared to before treatment, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in LogMAR visual acuity between before and after treatment ( χ2=84.229, P<0.001). LogMAR visual acuity improved at 1, 2, 4, 12, and 24 weeks after treatment compared to pretreatment, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in silk length of corneal perception between before and after treatment ( χ2=55.295, P<0.001). Silk length of corneal perception improved at 4, 12 and 24 weeks compared to pretreatment, and the differences were statistically significant (all at P<0.05). Baseline corneal defect severity grade was positively correlated with healing time ( β=10.55, P=0.032). Corneal defect diameter and area had no influence on the healing time ( β=-2.02, P=0.501; β=0.49, P=0.199). Conclusions:Autologous serum eye drop therapy is safe and effective for persistent corneal defects caused by NK.Re-application of autologous serum eye drops is still effective in individual patients with recurrent corneal defects after discontinuation of serum treatment.It can be combined with surgery for intractable cases.