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Introducción. La pandemia por COVID-19 afectó la atención de pacientes con diabetes mellitus tipo 1 (DM1). Además, se reportó un aumento de cetoacidosis diabética (CAD) como forma de diagnóstico. Objetivos. Evaluar si durante la pandemia por COVID-19 se modificaron el tiempo de evolución de síntomas, las causas de hospitalización por DM1 y la proporción de formas graves, y describir la infección por SARS-CoV-2 en estos pacientes. Población y métodos. Estudio transversal que incluyó pacientes menores de 19 años hospitalizados por DM1 en un centro pediátrico de referencia de marzo de 2018 a agosto de 2019 (prepandemia) y de marzo de 2020 a agosto de 2021 (pandemia). Resultados. Se analizaron 231 internaciones, 135 prepandemia y 96 en pandemia. Los pacientes con debut diabético presentaron menor tiempo de evolución de síntomas en pandemia que en prepandemia (18,8 ± 10,2 vs. 52,1 ±12,1 días, respectivamente; p <0,001). Las hospitalizaciones por todas las formas de debut diabético y el debut con CAD fueron más frecuentes en pandemia que en prepandemia (59,4 % vs. 39,3 %; OR 2,3; IC95% 1,3-3,8; p = 0,003); y (40,6 % vs. 20,7 %; OR 2,6; IC95% 1,4-5,2; p = 0,006) respectivamente. La proporción de formas graves de CAD no se modificó entre ambos períodos (48,1 % vs. 59,9 %; p = 0,3). Solo 6 pacientes presentaron infección por SARS-CoV-2; 3 fueron formas graves. Conclusión. Durante la pandemia, disminuyó el tiempo de evolución de síntomas y aumentó la frecuencia de hospitalizaciones por debut de DM1, con mayor proporción de CAD. No se modificó la proporción de formas graves de CAD
Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported. Objectives. To assess whether there were changes in the time from symptom onset, the causes of hospitalization due to DM1, and the proportion of severe forms, and to describe SARS-CoV-2 infection in these patients. Population and methods. Cross-sectional study in patients younger than 19 years hospitalized due to DM1 from March 2018 to August 2019 (pre-pandemic) and from March 2020 to August 2021 (pandemic). Results. The assessment included 135 hospitalizations in the pre-pandemic period and 96 during the pandemic. The time from symptom onset during the pandemic in those with debutof diabetes was shorter than in the pre-pandemic period (18.8 ± 10.2 versus 52.1 ± 12.1 days, respectively; p < 0.001). Hospitalizations due to all forms of diabetes debut and debut with DKA were more common during the pandemic than before it (59.4% versus 39.3%; odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.33.8; p = 0.003 and 40.6% versus 20.7%; OR: 2.6; 95% CI: 1.45.2; p = 0.006, respectively). Severe forms of DKA did not change between both periods (48.1% versus 59.9%; p = 0.3). Only 6 patients developed SARS-CoV-2 infection; 3 were severe. Conclusion. During the pandemic, the time from symptom onset decreased and the frequency of hospitalizations due to debut of DM1 increased. The proportion of severe forms of DKA did not change.
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Humans , Male , Female , Child, Preschool , Child , Adolescent , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/epidemiology , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Hospitalization/statistics & numerical data , Time Factors , Cross-Sectional StudiesABSTRACT
Abstract Background Neurofibromatosis type 1 (NF1) is a rare genetic disorder with a wide range of clinical manifestations, notably neurocutaneous features, that can lead to emotional and physical consequences. Objectives This study assessed the influence of sociodemographic factors and clinical features of the disease on the quality of life of Brazilian individuals with NF1. Methods This is a descriptive cross-sectional study. Data were collected from 101 individuals with NF1 using the Brazilian version of the Impact of NF1 on Quality of Life Questionnaire (INF1-QoL), a form with information on sociodemographic characteristics, and an NF1 visibility self-evaluation scale. The relationship between variables was evaluated through statistical testing, and the significance level was defined as 0.05. Results The study included 101 adults with NF1 aged 18 to 59 years, with a mean age of 35.54 years (±9.63) and a female predominance (n = 84, 83.17%). The mean total INF1-QoL score was 10.62 (±5.63), with a median of 10, minimum value of 0, and maximum of 31 points. Two characteristics of the participants were significantly associated with the quality of life: educational level (p = 0.003) and familial history of NF1 (p = 0.019). There was a statistically significant correlation between the INF1-QoL score and the degree of disease visibility (rho = 0.218; p = 0.028). Study limitations Cross-sectional study, conducted with a convenience sample and using self-reported measures. Conclusions The findings support the significant impact of NF1 on quality of life. The authors recommend multidisciplinary follow-up for patients, with adherence to anticipatory clinical care measures, adequate pain control, psychological assistance, and genetic counseling.
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La diabetes mellitus tipo 1 (DM1) es una enfermedad crónica autoinmune, con una incidencia creciente a nivel mundial. Los avances en el diagnóstico y en el tratamiento de los últimos años prolongaron la esperanza de vida, aumentando así el número de adultos con DM1. Se realizó un corte transversal que incluyó 201 personas adultas con diagnóstico de DM1, afiliados activos a la prepaga institucional de un hospital de alta complejidad de Argentina a Marzo de 2020. Se consignaron las siguientes variables: edad, sexo, comorbilidades, presencia de complicaciones, control glucémico y tratamiento farmacológico. Hubo un porcentaje similar de hombres y mujeres (51,2%), con una mediana de edad de 45 años (IIC 31-59). Un tercio de la población era mayor de 65 años. La mediana de evolución desde el diagnóstico fue de 14,5 años, y la mediana de último valor de hemoglobina glicosilada fue de 7,9%. Entre las complicaciones microvasculares más frecuentes se mencionan pie diabético (18%), retinopatía (6%) y nefropatía (2%). Un 4% presentó enfermedad cardiovascular (infarto agudo de miocardio, enfermedad coronaria, accidente cerebrovascular y/o enfermedad vascular periférica). El 88% recibía tratamiento con esquema intensificado de insulina y 6% usaban infusores de insulina. En relación al tratamiento con antidiabéticos orales, solo 11% recibían metformina, mientras que el uso de otros antidiabéticos orales fue inferior al 4%. En conclusión, este estudio proporciona valiosa información sobre las características de los adultos con DM1, dado que no hay demasiados estudios que aborden esta población (AU)
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease, with an increasing incidence worldwide. Advances in diagnosis and treatment in recent years have extended life expectancy, thus increasing the number of adults with T1DM. A cross-sectional study was conducted, including 201 adult individuals diagnosed with T1DM, active members of the institutional health plan of a high-complexity hospital in Argentina as of March 2020. The following variables were recorded: age, gender, comorbidities, presence of complications, glycemic control, and pharmacological treatment. There was a similar percentage of men and women (51.2%), with a median age of 45 years (IQR 31-59). One-third of the population was over 65 years old. The median duration since diagnosis was 14.5 years, and the median of the last glycated hemoglobin value was 7.9%. Among the most frequent microvascular complications, diabetic foot (18%), retinopathy (6%), and nephropathy (2%) were mentioned. 4% had cardiovascular disease (acute myocardial infarction, coronary artery disease, stroke, and/or peripheral vascular disease). 88% received treatment with intensified insulin regimens, and 6% used insulin pumps. Regarding treatment with oral antidiabetic drugs, only 11% received metformin, while the use of other oral antidiabetic drugs was less than 4%. In conclusion, this study provides valuable information about the characteristics of adults with T1DM, as there are not many studies that address this population (AU)
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Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/therapy , Cross-Sectional Studies , Hospital CareABSTRACT
Resumen Introducción: El síndrome de Miller-Dieker cuenta con un patrón de herencia autosómico dominante y pertenece al grupo de trastornos de la migración neuronal. Se caracteriza por la presencia de lisencefalia de tipo 1, retraso global del desarrollo, microcefalia, epilepsia y dismorfismos faciales dados por mutaciones en el cromosoma 17p13. El síndrome de Miller-Dieker es una enfermedad extremadamente rara con prevalencia de 1 caso por cada 100,000 recién nacidos vivos. Presentación de casos: Nosotros presentamos dos casos de síndrome de Miller-Dieker en los que datos de la exploración física y del interrogatorio fueron pistas que permitieron una fuerte sospecha diagnóstica y que a su vez el diagnóstico definitivo mediante FISH permitió brindar un adecuado manejo con la finalidad de mejorar el pronóstico a largo plazo. Conclusión: Se debe tener una alta sospecha diagnóstica mediante la exploración física dirigida a identificar alteraciones en pacientes con epilepsia de difícil control, ya que permite guiar el diagnóstico etiológico y con ello brindar un adecuado tratamiento.
Abstract Introduction: Miller-Dieker syndrome has an autosomal dominant pattern of inheritance and belongs to the group of neuronal migration disorders. It is characterized by the presence of type 1 lissencephaly, global development delay, microcephaly, epilepsy and facial dysmorphisms caused by mutations in chromosome 17p13. Miller-Dieker syndrome is an extremely rare disease with a prevalence of 1 case per 100,000 live births. Case presentation: We present two cases of Miller-Dieker syndrome in which data from the physical examination and questioning were clues that allowed a strong diagnostic suspicion and that, in turn, the definitive diagnosis by means of FISH allowed us to provide adequate management in order to improve the long-term prognosis. Conclusion: A high diagnostic suspicion must be achieved through physical examination aimed at identifying alterations in patients with difficult-to-control epilepsy, since it allows guiding the etiological diagnosis and thereby providing adequate treatment.
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Abstract Objectives: Clinical-laboratory comparison of a population of children and adolescents with DM1 followed at a Brazilian outpatient university clinic, at two different periods (2014 and 2020), regarding changes made both to the insulin therapy scheme and to the nutritional approach to carbohydrate counting. Methods: The data of patients with DM1 aged 0-19 years enrolled in the service in 2014 and 2020 were collected. Student's t-test was performed to compare the means of HbA1c and the variables of interest. Results: NPH + regular insulin was predominantly used in 2014 (49.1%), while in 2020, the predominance shifted to insulin analogs (48.4%). Pump use tripled from 1.3% in 2014 to 4.4% in 2020, and the percentage of patients performing carbohydrate counting reduced from 28.3% to 17.8%. Regarding HbA1c, the 2014 group of patients had a mean of 9.8%, while the 2020 group had a mean of 9.6% (p = 0.49). Conclusion: The change in treatments between 2014 and 2020 did not result in a significant improvement in HbA1c levels. However, it was identified the importance of carbohydrate counting and the use of insulin analogs to improve metabolic control in this population at both times.
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ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.
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Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.
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Neurofibromatosis type 1（NF1）is one of the most common autosomal dominant disorders. The disease is caused by mutations in the NF1 gene，which can involve multiple systems and have a variety of clinical manifestations，including café au lait macules，lisch nodules，neuroglioma，autism spectrum disorder，learning difficulties，neurofibromas，and skeletal dysplasia，et al.In previous studies on the pathogenesis of NF1，most of them have focused on the regulation of the RAS signaling pathway by neurofibromin. In recent years，researchers start exploring pathways other than RAS signaling to explore the potential functions of neurofibromin. This article reviews the research progress on the pathogenesis of NF1 in recent years，aiming to provide new ideas for treatment.
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Human herpes simplex virus type 1(HSV-1)infection of the upper respiratory tract is a common,mostly self-limiting disease.Reactivation of HSV-1 can sometimes cause lower respiratory tract infections.Coinfection of HSV-1 and other pathogens in the respiratory tract may cause severe diseases,resulting in HSV pneumonia and acute respiratory distress syndrome.This article reviews the symptoms and pathogenesis of HSV-1 infection or co-infections with other pathogens in the respiratory tract,as well as recent advances on drugs and vaccines for HSV-1.
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Herpes simplex viruses type 1(HSV1)is among the most ubiquitous human pathogens that cause a wide variety of disease states.The latent infection of the central nervous system and sporadically reactivation is the central part of HSV1 pathogenesis,which also brings challenges to antiviral therapies.At present,the mechanism of establishing,maintaining and reactivation of HSV1 has not been fully clarified,whereas it has been generally accepted that the epigenetic regulation may play an important role.Accumulating researches have also indicated that the lytic and latent viral genomes exhibit the different chromatin structures,and the accumulation of diverse post-translational modifies the histones endow viral genes with transcriptional activation or repression features.In addition,the latency-associate transcripts of virus may also participate in the genome epigenetic modification.In this review,we summarize the research progress of epigenetic regulation of HSV1 and highlight the critical role of chromatin remodeling in HSV1 lytic proliferation and establishment of latent infection.
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Objective To investigate the clinical and genetic characteristics of myotonic dystrophy type 1(DM1).Methods A DM1 patient and his family members admitted to the First Affiliated Hospital of Soochow University in May 2023 were examined by physical examination,EMG,muscle biopsy and genetic detection,and the family pedigree was drawn to analyze the clinical characteristics and genetic manifestations of the patients.Results There were 9 members in this family,2 of whom were suffering from DM1,and there was a phenomenon of genetic anticipation.Both patients with DM1 had typical symptoms such as myotonia and myasthenia,accompanied by involvement of multiple systems such as the central nervous system,heart,and endocrine system.The electromyogram showed characteristic myotonic potentials.Muscle biopsy of the proband showed typical myotonic dystrophy with rimmed vacuoles.Genetic detection found that their DMPK genes both had a large number of CTG trinucleotide repeat expansions.Oxcarbazepine treatment is effective.Conclusions DM1 is a genetic disease with typical symptoms of myotonia and myasthenia gravis,accompanied by involvement of central nervous system,heart,endocrine and other systems.Electromyography,muscle biopsy and gene detection can help to diagnose DM1.Rimmed vacuoles are rare in muscle pathology.Oxcarbazepine can improve the symptoms of myotonia.
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Objective:To develop an evaluation index system on health education effect for adolescents with type 1 diabetes mellitus (T1DM).Methods:Using "knowledge-attitude/belief-practice"model and health belief model as the theoretical framework, the first draft of the expert consulation questionnaire for evaluation index system on health education effect for adolescents with type 1 diabetes mellitus was drawn up through literature review, qualitative interview, and repeated discussions between groups. Two rounds of expert consultation were conducted. The results of the consulation were sorted and analyzed, the index structure, item content, and sequence were discussed repeatedly, and the evaluation index system on health education effect for adolescents with T1DM was determined, and the analytic hierarchy process was used to determine its weight.Results:A total of 21 female experts participated in two rounds of survey whose age was (43.48 ± 5.84) years old. The questionnaire response rates of the two rounds of expert consultations were 84.00%(21/25) and 85.71%(18/21), the authoritative coefficients were 0.96 and 0.97, the Kendall coordination were 0.181 and 0.256, respectively ( P<0.05). The consistency test of the weight of each indicator showed that the consistency ratios were all <0.1. The evaluation index system on health education effect for adolescents with T1DM was constructed with 5 first-level indicators (health knowledge, health belief, health practice, physiological indexes and health education satisfaction), 38 second-level indicators. Conclusions:The method used to construct the evaluation index system on health education effect for adolescents with T1DM was highly scientific and reliable, which provides the basis for clinical nurses to evaluate and monitor the effect of health education in adolescents with T1DM.
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BACKGROUND:Punicalagin has a wide range of effects and high safety,but its effect on osteoblasts and postmenopausal osteoporosis is unknown. OBJECTIVE:To investigate the effect of punicalagin on osteoblasts and postmenopausal osteoporosis. METHODS:The effect of punicalagin on the proliferation of MC3T3-E1 cells was detected.Punicalagin was added to the osteogenic induction medium to detect its effect on osteogenic differentiation.Punicalagin was used to treat ovariectomized rats and Micro CT scan and serum procollagen type 1 N-terminal propeptide test were performed after 3 months to detect the therapeutic effect. RESULTS AND CONCLUSION:Cell counting kit-8 assay showed that punicalagin could promote the proliferation of osteoblasts(P＜0.05).The results of qRT-PCR and western blot showed that punicalagin could promote the mRNA and protein expressions of alkaline phosphatase and Runx2 in osteoblasts(P＜0.05).The results of Micro CT scan and serological test showed that punicalagin could improve bone mineral density,bone volume fraction,trabecular thickness,trabecular number and procollagen type 1 N-terminal propeptide level of ovariectomized rats.To conclude,punicalagin can promote osteoblast proliferation and differentiation,and have therapeutic effects in postmenopausal osteoporosis rats.
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BACKGROUND:Exercise has been widely recognized in the prevention and treatment of diabetes.Aerobic exercise has become an important part of the treatment of type 1 diabetes.However,the effect of treadmill exercise on the metabolism and chronic neuroinflammation of type 1 diabetes in different sexes needs further discussion. OBJECTIVE:To study the effects of treadmill exercise on metabolism and chronic neuroinflammation in type 1 diabetes mice of different sexes. METHODS:Forty C57BL/6 mice were divided into male group and female group,with 20 mice in each group.Then,a diabetes model was established by continuous injection of streptozotocin at 80 mg/kg for 3 days.Ten rats from each group were randomly selected to perform 6-week treadmill exercise as the diabetes+exercise group and another 10 rats from each group were selected as the diabetes group.Serum sex hormones,liver tissue oxidative stress,brain tissue inflammatory factors,and liver pathology were detected,and Morris water maze was performed for the observation of behavioral changes in mice. RESULTS AND CONCLUSION:Compared with the diabetes group,the diabetes+exercise group delayed the rise of blood sugar in type 1 diabetes mice(P＜0.05)and showed a significant reduction in serum follicle-stimulating hormone,luteinizing hormone,liver superoxide dismutase,malondialdehyde,brain tumor necrosis factor α,interleukin-6 and interleukin-1β levels(P＜0.01),while serum estradiol,progesterone,estrogen,and liver glutathione peroxidase protein levels were significantly increased(P＜0.01,P＜0.05).Compared with male type 1 diabetes mice,female type 1 diabetes mice had significantly higher estradiol levels and lower luteinizing hormone levels(P＜0.05).Compared with the male diabetes+exercise group,the female diabetes+exercise group had lower liver glutathione peroxidase levels(P＜0.05).Compared with type 1 diabetes mice,the escape latency of exercise training mice was shorter(P＜0.01).In male mice,exercises significantly increased the time and platform crossing times of type 1 diabetes mice in the target quadrant(P＜0.01 or P＜0.05),while in female mice,exercises significantly increased the time of type 1 diabetes mice in the target quadrant(P＜0.05).Correlation analysis results showed that the levels of follicle-stimulating hormone,luteinizing hormone,progesterone,superoxide dismutase,malondialdehyde,tumor necrosis factor α,and interleukin-6 were positively correlated with the level of interleukin-1β(P＜0.05 or P＜0.01),whereas the levels of estradiol and progesterone were negatively correlated with the levels of superoxide dismutase,malondialdehyde,tumor necrosis factor α,interleukin-6 and interleukin-1β(P＜0.05 or P＜0.01).Overall,there are sex differences in the effects of treadmill exercise on metabolic indicators and chronic neuroinflammatory regulation in diabetes mice.Sex hormones are an important variable of treadmill exercise in the metabolic,inflammatory and cognitive responses in diabetes mice.
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AIM:To investigate the influence of fat mass and obesity-associated(Fto)gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM)mice,and to explore the mechanism of Fto gene underlying the calcium regulation.METHODS:Smooth muscle-specific Fto gene knockout(FtoSMKO)mice were generated using Cre-loxP technology.The experiment involved 3 groups of mice:wild-type(WT)group,DM model group and FtoSMKO-DM group,with 15 mice in each group.In DM group and FtoSMKO-DM group,type 1 DM was induced by intraperitoneal injec-tion of streptozotocin.The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution.The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multi-myograph system.The expression level of FTO protein in the aortic tissues was detected by Western blot.RESULTS:(1)Compared with WT mice,the expression levels of FTO protein in the aortic tissues of DM mice were significantly in-creased(P＜0.01).(2)The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P＜0.01).Compared with WT group,the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P＜0.05).There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P＞0.05).(3)The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group.Specifically,vaso-constriction responses mediated by non-L-type calcium channels and store-operated calcium channels(SOCC)were signifi-cantly enhanced in DM group.In addition,the responses mediated by inositol 1,4,5-trisphosphate receptors(IP3R),which facilitate calcium release from the sarcoplasmic reticulum,were significantly enhanced.However,the responses mediated by caffeine-activated ryanodine receptors(RyR),which also facilitate calcium release from the sarcoplasmic re-ticulum,were significantly inhibited(P＜0.05).(4)Compared with DM group,the phenylephrine-induced contraction re-sponses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P＜0.05).In particular,the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed(P＜0.05),while those mediated by caffeine-activated RyR were dramatically boosted(P＜0.05).However,IP3R-mediated responses were not affected(P＞0.05).CONCLUSION:Smooth muscle-specific Fto gene knockout suppresses contractile hyperre-sponsiveness in the aortic smooth muscle of DM mice,which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle.
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Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that commonly affects adolescents, characterized by progressive destruction of pancreatic β-cells, absolute insulin deficiency, and hyperglycemia. The pathogenesis of type 1 diabetes mellitus is complex and is believed to be mainly associated with immunity, environment, and genetics. There is increasing evidence that gut microbiota is closely related to the occurrence of type 1 diabetes mellitus. This article focuses on the immune mechanisms and roles of gut microbiota and its derivatives in the development of type 1 diabetes mellitus from the perspectives of innate and adaptive immunity. Additionally, it introduces therapeutic approaches targeting gut microbiota for the treatment of type 1 diabetes mellitus.
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BackgroundDiabetes distress is highly prevalent and has adverse impacts in adolescent patients with type 1 diabetes. However， the related factors of diabetes distress in adolescents with type 1 diabetes are not clear. ObjectiveTo identify the factors associated with diabetes distress in adolescents with type 1 diabetes using Meta-analysis， and to provide a scientific evidence for effective prevention and improvement of diabetes distress in adolescents with type 1 diabetes. MethodsOn December 1， 2022， a computerized search was conducted on databases including PubMed， Cochrane Library， Web of Science， Embase， CNKI， Wanfang Data， VIP and China Biomedical Literature Database， and studies relevant to diabetes distress in adolescents with type 1 diabetes were systematically included. Quality assessment of cross-sectional and cohort studies was carried out using criteria defined by the Agency for Healthcare Research and Quality （AHRQ） and Newcastle-Ottawa Scale （NOS）. Then the included studies were pooled in a Meta-analysis using Revman 5.3. ResultsA total of 22 studies were included， involving 6 442 adolescents with type 1 diabetes. Meta-analysis denoted that the occurrence of diabetes distress among adolescents with type 1 diabetes was correlated with age （r=0.094，95% CI： 0.042~0.145）， HbA1c （r=0.291， 95% CI： 0.248~0.335）， trait anxiety （r=0.585， 95% CI： 0.526~0.639）， depressive symptoms （r=0.635， 95% CI： 0.590~0.676）， resilience （r=-0.410， 95% CI： -0.528~-0.276） and parents' diabetes distress （r=0.462， 95% CI： 0.421~0.501）. ConclusionFactors including age， HbA1c， trait anxiety， depressive symptoms， resilience and parents' diabetes distress are correlated with diabetes distress in adolescents with type 1 diabetes. ［Funded by Sichuan Science and Technology Program （number， 24KJPX0034）］
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【Objective】 To establish strategies for preventing and managing hypoglycemia in children and adolescents with type 1 diabetes, in order to provide a clinical practice basis for reducing the incidence of hypoglycemia and optimizing comprehensive blood sugar management. 【Methods】 All domestic and foreign evidence on the prevention and management of hypoglycemia in children was retrieved until August 2023, including clinical practice guidelines, evidence summaries, best practice information books, expert consensus, systematic reviews, and original studies. 【Results】 This study included 9 articles, comprising 3 practical guidelines, 4 expert consensus articles, 1 clinical decision, and 1 evidence summary, covering 9 aspects ranging from hypoglycemia identification, risk factors, blood sugar monitoring, insulin treatment plans, health education, diet, exercise, and psychological support. It presents a total of 34 pieces of evidence, synthesizing the best evidence from both domestic and international sources on hypoglycemia prevention strategies for children and adolescents with type 1 diabetes. 【Conclusion】 Based on the latest evidence from domestic and global sources, this study systematically illustrates prevention strategies for hypoglycemia in children and adolescents with type 1 diabetes, providing comprehensive evidence and a reliable theoretical basis for raising clinical caregivers′ awareness of hypoglycemia prevention, reducing the risk of hypoglycemia occurrence, and constructing a systematic hypoglycemia prevention and control strategy.
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ObjectiveTo explore the potential molecular mechanism of Qizhu Kang'ai Formula （芪术抗癌方， QZKAF） for the treatment of colorectal cancer （CRC）. MethodsNetwork pharmacology was used to analyze the active ingredients and targets of QZKAF for CRC， and analyze the key targets of QZKAF for the treatment of CRC by gene function annotation （GO） and Kyoto Encyclopedia of Genomes （KEGG） pathway enrichment analysis. Molecular docking was applied to predict the binding activity of the core active ingredients to the key targets. A orthotopic transplantation tumor mice model of CRC was established to validate the key targets of QZKAF for CRC obtained from network pharmacology analysis. Forty-eight mice were randomly divided into the sham operation group， the model group， the 5-fluorouracil （5-Fu） group， and the QZKAF low-， medium-， and high-dose groups， with 8 mice in each group. Except for the sham operation group， the remaining groups underwent colon cancer orthotopic transplantation tumor modeling. The 5-Fu group was given 30 mg/kg of 5-Fu by intraperitoneal injection once every 3 days on the alternate day after modeling， while the QZKAF low-， medium-， and high-dose groups were given 2.925， 5.85， and 11.7 g/（kg·d） of QZKAF by gastric gavage， respectively， and the sham-operation group and the model group were gavaged with 0.1 ml/10 g of normal saline every day， all for 21 days. The in situ tumors mass and the number of liver metastases were compared between the groups. The pathological changes of colon tumor tissues were observed by HE staining， and the protein expression of protein tyrosine phosphatase nonreceptor type 1 （PTPN1）， vinculin， integrin subunit αν， integrin subunit β3， and E-cadherin were detected in colon tumor tissues by Western blot. ResultsNetwork pharmacology screening yielded that the top six core active ingredients of QZKAF intervening in CRC were quercetin， kaempferol， apigenin， luteolin， baicalein and ursolic acid. There were 212 targets of action， and the ranked top three were prostaglandin endoperoxide synthase 1 （PTGS1）， prostaglandin endoperoxide synthase 2 （PTGS2）， and PTPN1， which may be the key targets of QZKAF in the treatment of CRC. These key targets were significantly enriched mainly in phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway， focal adhesion and adhesion junction. Molecular docking results： except for PTGS1 with better binding activity to quercetin， kaempferol， and apigenin （binding energy ≥-7.0 kcal/mol）， PTGS1 showed strong binding activity to lignans， baicalein， ursolic acid， as well as PTGS2 and PTPN1 to the six core active ingredients （binding energy ＜-7.0 kcal/mol）. Experimental validation results： the protein expression of PTPN1， vinculin， integrin subunit αν， integrin subunit β3 in the colon tumor tissues of mice in the model group significantly increased， and the expression of E-cadherin significantly decreased compared to those in the sham operation group （P＜0.05）. Compared to those in the model group， the mass of the in situ tumors was reduced， and the number of hepatic metastasis nodules decreased in the high- and medium-dose QZKAF groups （P＜0.05）； the expression levels of PTNP1， vinculin， integrin subunit αν， integrin subunit β3 and E-cadherin in all QZKAF groups and 5-Fu group showed different degrees of retracement， and the changes of the indicators in all QZKAF groups showed a certain degree of dose-dependence （P＜0.05）. HE staining showed that the nuclei of tumor cells in the model group were mostly schizophrenic， and there were different degrees of nuclear fragmentation of tumor cells in all QZKAF groups with more in the medium- and high-dose groups. ConclusionQZKAF could inhibit the growth of in situ tumors and liver metastasis of CRC. Its mechanism might be related to the regulation of tumor cell-cell and tumor cell-extracellular matrix adhesion by PTPN1.
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Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.