Structural and functional damage to the hippocampal neurovascular unit in diabetes-related depression

Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression.

Effects of α-zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy

Objective: To study the effects of -zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy. Methods: A total of 90 patients with type 2 diabetes peripheral neuropathy in our hospital from September 2015 to September 2018 were enrolled in this study. The subjects were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group were treated with -zinc sulfate, the treatment group were treated with -zinc sulfate combined with yiqiyangyinghuoxue therapy, the two groups were treated for 3 months. The serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before treatment. After treatment, the serum NSE, UA, Hcy, hs-CRP, HMGB1, CysC, TGF-β1, ESM-1 and plasma ET, TNF of the two groups were significantly lower than before treatment, the serum BDNF, 25-(OH)D3, NO of the two groups were significantly higher than before treatment, and that of the treatment group after treatment were significantly better than the control group. Conclusion: α-zinc sulfate combined with yiqiyangyinghuoxue therapy on patients with type 2 diabetes peripheral neuropathy has a good efficacy, can improve the neuropathy and vascular endothelial damage, improve related factors, and it was worthy clinical application.

Dietary Patterns and Their Association with Depression among Type 2 Diabetes Patients in Gaza Strip, Palestine

Background: Depression is a common mental disorder. Globally, more than 340 million people of all ages suffer from depression. The aim of our study was to determine the association between major dietary patterns and depression among type 2 diabetes patients. Methods: This cross-sectional study was conducted among 480 type 2 diabetes patients attending primary healthcare centers in Gaza Strip, Palestine. The depression, anxiety, stress scales (DASS, 21-items) questionnaire was used to measure the score of depression. The participants’ demographic, socioeconomic and medical history data was collected and the 98-items semi-quantitative food frequency questionnaire was used for evaluating the dietary patterns. Statistical analysis was performed using SPSS version 20. Results: Based on depression scale, 29.0% of type 2 diabetes patients had depression, (58.3% females, and 41.7% males). The prevalence of mild, moderate, severe, and very severe depression was 11.7%, 8.5%, 6.7%, and 2.1%, respectively. Furthermore, two major dietary patterns were identified by factor analysis: The Western, and the grains-vegetables, and fruits patterns. After adjusting for the potential confounders, patients in the lowest tertile (T1) of the grains-vegetables, and fruits dietary pattern had a lower odds for depression (OR 0.763 95% CI (0.667 - 0.871), P value = 0.001);where as a higher odds for healthy (OR 1.443 95% CI (1.131 - 1.839), P value = 0.004), compared to those in the highest tertile (T3). Conclusion: The grains-vegetables, and fruits dietary pattern may be associated with a lower prevalence of depression, and has been shown to be the healthiest dietary pattern among type 2 diabetes patients.

Gestational diabetes from A to Z

Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.

Analysis of factors related to postpartum depression in pregnancyinduced hypertension syndrome patients and construction and evaluation of nomograms

BACKGROUND It is positive to integrate and evaluate the risk factors for postpartum depression in patients with pregnancy-induced hypertension syndrome and to detect highrisk patients as early as possible,which has application value for the clinical development of personalized prevention programs and prognosis of patients.AIM To analyze factors related to postpartum depression in patients with pregnancyinduced hypertension and construct and evaluate a nomogram model.METHODS The clinical data of 276 patients with pregnancy-induced hypertension admitted to Huzhou Maternity and Child Health Care Hospital between January 2017 and April 2022 were retrospectively analyzed.We evaluated the depression incidence at 6 wk postpartum.The depression group included patients with postpartum depression,and the remainder were in the non-depression group.Multivariate logistic regression analysis and the LASSO regression model were applied to analyze the factors related to postpartum depression in patients with pregnancyinduced hypertension.After that,a risk prediction model nomogram was constructed and evaluated.RESULTS Multivariate logistic regression analysis showed that vitamin A deficiency(VAD)during pregnancy and puerperium,family history of hypertension,maternal intestinal flora imbalance,eicosapentaenoic acid(EPA),and docosahexaenoic acid(DHA)were independent risk factors for postpartum depression in patients with pregnancy-induced hypertension(P<0.05).We constructed the nomogram model based on these five risk factors.The area under the curve,specificity,and sensitivity of the model in predicting postpartum depression in patients with pregnancy-induced hypertension was 0.867(95%confidence interval:0.828–0.935),0.676,and 0.889,respectively.The average absolute error was 0.037(Hosmer-Lemeshow testχ2=10.739,P=0.217).CONCLUSION VAD during pregnancy and puerperium,family history of hypertension,maternal intestinal flora imbalance,EPA,and DHA affect postpartum depression in patients with pregnancy-induced hypertension.

Psychological status and diabetes-related distress of Chinese type 1 diabetes patients in Jiangsu province, China

We sought to assess the psychological status and diabetes-related distress of Chinese type 1 diabetes patients in Jiangsu province, China. According to the World Health Organization criteria, 42 patients with type 1 diabetes were enrolled in the study and assessed with the Self-Rating Anxiety Scale （SAS）, Self-Rating Depression Scale （SDS） and Diabetes Distress Scale （DDS）. All data were tabulated and statistical analyses were performed. The study summarized cases of 42 patients with type 1 diabetes, including 17 males and 25 females with a mean age of 23- 12 years and a mean duration of diabetes of 7_ 6 years. Compared to the Chinese normative data, the SAS standard score was significantly higher, whereas SDS standard score had no statistical significance. The SAS standard score was most highly correlated with diabetes duration （y = 0.547, P = 0.011）. Additionally, 19.5% of the patients had moderate or even severe diabetes-related distress and 21.4% had moderate or even severe emo- tional burden while 26.2% had regimen-related distress. Multiple stepwise regression analysis showed that the mean correlation between DDS and the four domains was high, particularly the emotional burden domain （esti- mated D = 0.363, P 〈 0.001） and regimen-related distress domain （estimated 13 = 0.356, P 〈 0.001）. The correlation between SAS and DDS was positive （estimated 13 = 0.039, P = 0.027）. In conclusion, the results showed the im- portance of psychological aspects in Chinese individuals with type 1 diabetes. Screening and treatment of psycho- logical aspects may result in better adherence and increased quality of life for patients with diabetes.

Does parity worsen diabetes-related chronic complications in women with type 1 diabetes?

AIM: To determine the relationship between parity, glycemic control, cardiovascular risk factors and diabetesrelated chronic complications in women with type 1 diabetes.METHODS: This was a multicenter cross-sectional study conducted between December 2008 and December 2010 in 28 public clinics in 20 cities from the 4 Brazilian geographic regions. Data were obtained from 1532 female patients, 59.2% Caucasians, and aged 25.2 ± 10.6 years. Diabetes duration was of 11.5 ± 8.2 years. Patient's information was obtained through a questionnaire and a chart review. Parity was stratified in five groups: Group 0(nulliparous), group 1(1 pregnancy), group 2(2 pregnancies), group 3(3 pregnancies), group 4(≥ 4 pregnancies). Test for trend and multivariate random intercept logistic and linear regression models were used to evaluate the effect of parity upon glycemic control, cardiovascular risk factors and diabetes-related complications. RESULTS: Parity was not related with glycemic control and nephropathy. Moreover, the effect of parity upon hypertension, retinopathy and macrovascular disease did not persist after adjustments for demographic and clinical variables in multivariate analysis. For retinopathy, the duration of diabetes and hypertension were the most important independent variables and for macrovascular disease, these variables were age and hypertension. Overweight or obesity was noted in a total of 538 patients(35.1%). A linear association was found between the frequency of overweight or obesity and parity(P = 0.004). Using a random intercept multivariate linear regression model with body mass index(BMI) as dependent variable a borderline effect for parity(P = 0.06) was noted after adjustment for clinical and demographic data. The observed variability of BMI was not attributable to differences between centers.CONCLUSION: Our results suggest that parity has a borderline effect on body mass index but does not have an important effect upon hypertension and micro or macrovascular chronic complications. Future prospective evaluations must be conducted to clarify the relationship between parity, appearance or worsening of diabetesrelated chronic complications.

Study on Related Factors of Aspirin Resistance in Acute Ischemic Stroke

Objective:To study the related factors of aspirin resistance(AR)in acute ischemic stroke.Methods:A total of 138 patients with acute ischemic stroke treated in hospital affiliated to Xuzhou medical university from August 2016 to August 2018 were the study subjects,examine his medical data from the past.They were divided into the AR group(40 cases)and the non-AR group(98 cases)according to whether AR appears.Gender,disease history,biochemical indicators and etc.were compared between the two groups.The independent risk factors of AR were investigated using univariate analysis and logistic regression analysis.Results:40 cases of AR occurred in 138 patients,with an incidence rate of 28.99%.Diabetes,platelet count(PLT),microRNA-19a(m iR-19a)expression,smoking,high-sensitivity C-reactive protein(hs-CRP),Low-density lipoprotein cholesterol(LDL-C),fibrinogen(FIB)and age difference between the AR group and non-AR group was statistically significant(P<0.05).Gender,hypertension,uric acid(UA),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),homocysteine(Hcy),total cholesterol(TC),and alanine aminotransferase(ALT)between the two groups were not significantly different(P>0.05).Logistic regression analysis showed that the independent risk factors for AR in acute ischemic stroke were diabetes(OR=2.773,95%CI:1.102~5.065,P=0.025),miR-19a(OR=3.021,95%CI:1.322~6.545,P=0.021),hs-CRP(OR=2.719,95%CI:1.301~5.022,P=0.028)and smoking(OR=1.983,95%CI:1.114~3.887,P=0.040).Conclusion:The incidence of AR is higher in acute ischemic stroke.Risk factors include diabetes,miR-19a expression,hs-CRP,smoking,etc.Clinical intervention measures can be taken to reduce the risk of AR and improve acute ischemic stroke prognosis.

Why do we not reverse the path?Stress can cause depression,reduction of brain-derived neurotrophic factor and increased inflammation

The aim of this paper is to describe the direction of the link between stress,depression,increased inflammation and brain-derived neurotrophic factor(BDNF)reduction.We hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of depression.Both stress and depression,if not resolved over time,activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into cytokines.This cascade fosters systemic chronic inflammation and reduced plasma BDNF levels.Since people with depression have a 60%increased risk of developing type 2diabetes(T2D)and show high levels of inflammation and low levels of BDNF,we hypothesize possible reasons that might explain why T2D,depression and dementia are often associated in the same patient.

Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors

Although several previous studies have been published on the effects of dipeptidase-4(DPP-4) inhibitors in diabetic hemodialysis(HD) patients, the findings have yet to be reviewed comprehensively. Eyesight failure caused by diabetic retinopathy and aging-related dementia make multiple daily insulin injections difficult for HD patients. Therefore, we reviewed the effects of DPP-4 inhibitors with a focus on oral antidiabetic drugs as a new treatment strategy in HD patients with diabetes. The following 7 DPP-4 inhibitors are available worldwide: sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin, and saxagliptin. All of these are administered once daily with dose adjustments in HD patients. Four types of oral antidiabetic drugs can be administered for combination oral therapy with DPP-4 inhibitors, including sulfonylureas, meglitinide, thiazolidinediones, and alpha-glucosidase inhibitor. Nine studies examined the antidiabetic effects in HD patients. Treatments decreased hemoglobin A1 c and glycated albumin levels by 0.3% to 1.3% and 1.7% to 4.9%, respectively. The efficacy of DPP-4 inhibitor treatment is high among HD patients, and no patients exhibited significant severe adverse effects such as hypoglycemia and liver dysfunction. DPP-4 inhibitors are key drugs in new treatment strategies for HD patients with diabetes and with limited choices for diabetes treatment.

Psychological themes that influence self-management of type 1 diabetes

It has long been accepted that psychological factors adversely influence efforts to optimise glycaemic control.These are often unrecognised in terms of clinical assessment and therefore under reported.This essay presents an introduction to psychological issues that interact with psychiatric co-morbidities and diabetesspecific distress,and a case scenario illustrating the interconnectedness of presenting problems and themes.In the way that we cannot separate carbohydrate counting,blood glucose monitoring and insulin doseadjustment in the understanding of a presenting problem such as poor control,so we cannot separate the concurrent thoughts,feelings,and behaviours.Each of these emotional aspects are self-managed either through avoidance,or by delayed disclosure and are frequently associated with poor health outcomes.There is a requirement for the healthcare team to be sensitised to these issues and to develop styles of communication that are empathic,reflective and non judgemental.A brief outline of evidence-based psychotherapy treatments is given.

Analysis of anxiety and depression status and their influencing factors in patients with diabetic retinopathy

BACKGROUND Diabetic retinopathy(DR)is a common complication of diabetes and the leading cause of visual impairment and blindness.It has a serious impact on the mental and physical health of patients.AIM To evaluate the anxiety and depression status of patients with DR,we examined their influencing factors.METHODS Two hundred patients with DR admitted to the outpatient and inpatient departments of ophthalmology and endocrinology at our hospital were selected.A questionnaire was conducted to collect general patient information.Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Sevenitem Generalized Anxiety Disorder scale,respectively.The diabetes specific quality of life scale and Social Support Rating Scale were used to assess the quality of life of patients with DR and their social support,respectively.Logistic regression analysis was used to assess the correlations.RESULTS The prevalence of depression and anxiety were 26%(52/200)and 14%(28/200),respectively.Regression analysis revealed that social support was associated with depression[odds ratio(OR)=0.912,95%confidence interval(CI):0.893-0.985]and anxiety(OR=0.863,95%CI:0.672-0.994).Good quality of life(diabetes specific quality of life scale score<40)was a protective factor against anxiety(OR=0.738,95%CI:0.567-0.936)and depression(OR=0.573,95%CI:0.4566-0.784).Visual impairment significantly increased the likelihood of depression(OR=1.198,95%CI:1.143-1.324)and anxiety(OR=1.746,95%CI:1.282-2.359).Additionally,prolonged diabetes duration and history of hypertension were significant risk factors for both conditions,along with a family history of diabetes.CONCLUSION Key factors influencing anxiety and depression in patients with DR include social support,quality of life,visual impairment,duration of diabetes,family history of diabetes,and history of hypertension.

Depressive symptoms and associated factors among renal-transplant recipients in China

Aim:This study aimed to explore depressive symptoms and associated factors among renal-transplant(RT)recipients in China.Methods:This study included 287 RT recipients.Data were collected from August to November 2014 by utilizing demographic forms,namely,the Self-rating Depression Scale and the Multidimensional Scale of Perceived Social Support.Descriptive statistics,Student's t test,Chi-square test,ANOVA,and multiple linear regression were used for data analysis.Results:More than half of the recipients presented depressive symptoms.All recipients in the four transplant period groups(≤5 yr,5e10 yr,10e15 yr,and>15 yr)reported greater depressive symptoms than the Norm.No significant difference was observed in the depressive symptoms in the four transplant period groups.Multiple linear regression indicated that depressive symptoms were significantly associated with employment status,economic burden,inhabitation area,and social support.Conclusion:Depression is common among RT recipients in China.Employment status,economic burden,inhabitation area,and social support are the main factors affecting depression among RT recipients.Follow-up clinics should prescribe the evaluation of depression as a routine examination for RT patients.Moreover,depressed recipients must be provided with individualized care by collecting information on the depressive symptoms,employment status,economic burden,inhabitation area,and perceived social support of recipients.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

脑梗死患者康复科住院期间卒中后抑郁程度的相关因素

目的 探讨脑梗死患者在康复科住院期间发生卒中后抑郁的相关危险因素。方法 回顾性分析2019年12月至2023年2月在北京博爱医院住院、曾诊断为抑郁状态且经心理科会诊的脑梗死患者,统计一般资料(性别、年龄、学历、婚姻),疾病特征(病程、病灶位置、偏瘫侧别、感觉障碍、失语、失眠、吞咽障碍、肩手综合征、便秘),运动功能(偏瘫侧肌力、Brunnstrom分期),简易精神状态检查(MMSE)、美国国立卫生研究院卒中量表(NIHSS)、Fugl-Meyer评定量表(FMA)、Fugl-Meyer评定量表-平衡(FMA-B)、改良Barthel指数(MBI)、汉密尔顿抑郁量表(HAMD)评分等资料。HAMD≤20分的患者入低HAMD组,HAMD> 20分的患者入高HAMD组。结果 在2 403例脑梗死患者中,诊断为抑郁状态且经心理科会诊的患者269例,低HAMD组103例,高HAMD组166例。高HAMD组便秘发生率较低,吞咽障碍、肩手综合征发生率较高(χ^(2)> 5.379, P <0.05);髂腰肌、股四头肌肌力,下肢和手Brunnstrom分期,NIHSS、MMSE、FMA、FMA-B、MBI评分差于低HAMD组(|Z|> 2.020, t> 2.171, P <0.05)。Logistic回归分析显示,便秘(OR=0.435)、股四头肌肌力(OR=0.782)、吞咽障碍(OR=2.602)是康复期患者发生卒中后抑郁的相关因素(P <0.05)。结论 卒中后吞咽障碍和肌力下降,可能加重卒中后抑郁。便秘可能并不加重卒中后抑郁程度。

血清CysC和CTRP9水平对2型糖尿病视网膜病变的诊断价值

目的探讨血清胱抑素C(CysC)和C1q肿瘤坏死因子相关蛋白9(CTRP9)水平对2型糖尿病患者糖尿病视网膜病变(DR)及糖尿病黄斑水肿(DME)的诊断价值。方法采用横断面研究方法,纳入2021年4月至2022年4月在甘肃省人民医院就诊的135例2型糖尿病患者,年龄45~75岁,按照DR分级标准将患者分为无DR(NDR)组、非增生型DR(NPDR)组和增生型DR(PDR)组,每组45例。根据有无DME将NPDR组和PDR组患者分为DME组51例和非DME组39例。另选取45名健康体检者作为正常对照组。采集受检者空腹外周静脉血,检测血清中糖化血红蛋白、空腹血糖、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、CysC和CTRP9水平。比较各组CysC和CTRP9表达差异。采用多因素Logistic回归分析模型评估DR及DME的独立影响因素,采用受试者工作特征(ROC)曲线评价血清CysC和CTRP9对DR及DME的诊断价值。结果正常对照组、NDR组、NPDR组和PDR组血清CysC水平分别为0.74(0.67,0.83)、1.03(0.85,1.22)、1.40(0.98,1.63)和1.66(1.31,1.85)mg/L,呈逐渐升高趋势;CTRP9水平分别为(136.90±14.95)、(120.23±16.31)、(109.50±14.71)和(90.99±13.88)pg/ml,呈逐渐降低趋势;组间总体比较差异均有统计学意义(Z=89.430,P<0.001;F=74.242,P<0.001),组间两两比较差异均有统计学意义(均P<0.05)。与非DME组相比,DME组血清CysC水平显著升高、CTRP9水平显著降低,差异均有统计学意义(均P<0.05)。多因素Logistic回归分析结果显示,血清CysC(OR=19.742,95%CI:4.515~86.316,P<0.001)是DR发生的独立危险因素,CTRP9水平(OR=0.937,95%CI:0.908~0.966,P<0.001)是DR发生的保护因素;血清CTRP9水平(OR=0.838,95%CI:0.778~0.903,P<0.001)为DME发生的保护因素。ROC曲线结果显示,血清CysC和CTRP9水平单独及联合诊断2型糖尿病患者并发DR的ROC曲线下面积(AUC)分别为0.798、0.802和0.870,血清CysC和CTRP9水平截断值分别取1.34 mg/L和110.12 pg/ml时可获得最佳诊断效能;其单独及联合诊断DR患者并发DME的AUC分别为0.682、0.923和0.923,血清CTRP9水平的截断值取104.68 pg/ml时可获得最佳诊断效能。结论血清CysC水平升高及CTRP9水平降低是2型糖尿病患者发生DR的危险因素,血清CTRP9水平降低为DR患者发生DME的危险因素之一。

丹酚酸B对2型糖尿病小鼠心肌病氧化应激的作用及机制

目的探讨丹酚酸B(Sal B)对2型糖尿病小鼠心肌病(DCM)氧化应激的作用及潜在机制。方法60只C57BL/6J小鼠分为空白组(n=12,Control组,正常饲料,灌胃生理盐水)和高脂高糖(HG)组[n=48,HFG组,链脲佐菌素(STZ)联合HFG饲料构建DCM模型],造模成功的HFG组小鼠分为DCM组(灌胃生理盐水)、Sal B低剂量[1.50 mg/(kg·d)]组(Sal B.L组)、Sal B高剂量[3.00 mg/(kg·d)]组(Sal B.H组)及200 mg/(kg·d)二甲双胍治疗组(Metformin组),灌胃连续8周;麻醉各组小鼠,采用小动物超声仪检测仰卧位时各组小鼠心脏的左室射血分数(LVEF)、缩短分数(FS)、左室收缩末期容积(LVESV)及左室收缩期末期内径(LVIDs);处死各组小鼠,取心脏制作切片、苏木素-伊红(HE)和Masson染色观察心肌组织形态学特征;采用试剂盒检测各组小鼠心肌组织中细胞丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽(GSH)的水平,采用Western blot分析氧化应激蛋白Kelch样ECH关联蛋白1(Keap1)、核因子-E2相关因子2(Nrf2)、磷酸化Nrf2(pNrf2)、过氧化物酶1(PRDX1)、血红素加氧酶1(HO-1)及凋亡相关蛋白活化的半胱氨酸蛋白(Cleaved-caspase3)、B淋巴细胞瘤-2蛋白(Bcl2)、Bcl2关联X(bax)蛋白的表达;SD乳鼠心脏提取分离培养原代新生大鼠心肌细胞(PNRCMs)构建DCM体外模型,将PNRCMs分为40 mmol/L甘露醇(Mannitol)组、空白(Control)组、40 mmol/L HG(HG)组、40 mmol/L HG+25μmol/L Sal B(Sal B低剂量,Sal B.L)组、40 mmol/L HG+50μmol/L Sal B(Sal B高剂量,Sal B.H)组、40 mmol/L HG+0.25 mmol/L二甲双胍(Metformin)组,检测各组细胞的活性氧(ROS)、MDA、SOD及GSH水平,采用Western blot检测氧化应激蛋白Keap1、Nrf2、pNrf2、PRDX1、HO-1及凋亡相关蛋白Cleaved-caspase3、bax、Bcl2蛋白的表达;采用实时定量反转录聚合酶链式反应(RT-qPCR)法检测氧化应激相关基因Keap1、Nrf2、PRDX1及HO-1信使RNA(mRNA)的表达;采用Nrf2抑制剂(ML385)和激动剂(甲基巴多索隆)进一步分析氧化应激蛋白Keap1、Nrf2、pNrf2、PRDX1及HO-1的表达。结果与Control组比较,DCM组小鼠的LVEF、FS降低(P<0.01),LVESV、LVIDs升高(P<0.01),心肌组织排列紊乱、间质细胞增多并伴有炎性细胞浸润及胶原沉积,心肌组织中MDA含量增加、SOD和GSH减少(P<0.01),心肌组织中Keap1、Cleaved-caspase3及bax蛋白表达上调,Nrf2、pNrf2、PRDX1、HO-1及Bcl2蛋白表达下调(P<0.01);与Control组比较,HG组心肌细胞中ROS表达增加,SOD表达下降(P<0.05),MDA含量增加、GSH表达下降(P<0.01),心肌细胞中的Keap1、Cleaved-caspase3及bax蛋白表达增加(P<0.01),Nrf2、pNrf2、PRDX1、HO-1及Bcl2蛋白表达下降(P<0.01),心肌细胞中的Keap1 mRNA表达升高(P<0.05),Nrf2、PRDX1及HO-1 mRNA表达降低(P<0.05);与DCM组比,Sal B.L和Sal B.H组小鼠的LVEF、FS增加(P<0.01)、LVESV、LVIDs降低(P<0.01),心肌组织排列整齐、炎性细胞浸润减少、心肌胶原沉积减少,心肌组织中MDA含量减少、SOD和GSH含量增加(P<0.01),心肌组织中Keap1、Cleaved-caspase3及bax表达下调,Nrf2、pNrf2、PRDX1、HO-1及Bcl2蛋白表达上调(P<0.05);与HG组相比,Sal B.L和Sal B.H量组心肌细胞中ROS表达、MDA含量减少,SOD和GSH含量增加(P<0.05),心肌细胞中的Keap1、Cleaved-caspase3及bax蛋白表达减少(P<0.05),Nrf2、pNrf2、PRDX1、HO-1及Bcl2表达增加(P<0.05);心肌细胞中的Keap1 mRNA表达降低(P<0.05),Nrf2、PRDX1和HO-1 mRNA表达升高(P<0.05);进一步采用Nrf2抑制剂ML385和激动剂甲基巴多索隆干预,与HG组相比,Sal B.H组心肌细胞中的Nrf2、pNrf2、PRDX1及HO-1表达增加(P<0.05);与Sal B.H组相比,ML385和Sal B联用组心肌细胞中的Nrf2、pNrf2、PRDX1及HO-1的表达减少(P<0.05)。结论Sal B可降低2型糖尿病小鼠DCM的氧化应激作用,其机制与Keap1/Nrf2信号通路蛋白的表达有关。

孕早期血清脂肪因子CTRP6与妊娠糖尿病的关系

目的研究孕早期妇女血清补体C1q/肿瘤坏死因子相关蛋白6(C1q/tumor necrosis factor-related protein 6,CTRP6)的表达水平,探讨其与妊娠糖尿病(gestational diabetes mellitus,GDM)的关系。方法前瞻性连续选取2021年3月至2022年3月在郑州大学第二附属医院门诊产检的孕10~13周孕妇,收集孕妇的年龄、身高、体质量、末次月经时间,检测孕早期总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白(high density lipoprotein,HDL)、低密度脂蛋白(low density lipoprotein,LDL)、空腹血糖(fasting plasma glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、CTRP6水平,计算孕前体质量指数(body mass index,BMI)、基线BMI、产前BMI和胰岛素抵抗指数(亦称胰岛素抵抗的稳态模型评估,homeostatic model assessment of insulin resistance,HOMA-IR)。所有孕妇均于孕24~28周行75g口服葡萄糖耐量试验,根据试验结果分为GDM组和糖耐量正常(normal glucose tolerance,NGT)组。比较两组孕妇孕早期的临床资料及实验室指标,分析孕早期血清CTRP6与各指标的相关性及其与GDM的关系。结果共纳入孕妇213例,完整随访203例,其中52例孕妇被诊断为GDM,GDM发病率25.62%。GDM组孕妇的孕早期血清CTRP6、年龄、孕前BMI、基线BMI、产前BMI、TC、LDL、FPG、HbA1c、FINS、HOMA-IR均较NGT组升高,差异有统计学意义(P<0.05)。孕早期CTRP6与年龄、孕前BMI、基线BMI、产前BMI、TG、LDL、FPG、HbA1c、FINS、HOMA-IR呈正相关,与HDL呈负相关(P<0.05)。校正年龄、BMI、糖脂代谢指标及HOMA-IR后,孕早期CTRP6为GDM发病的独立影响因素。结论孕早期血清CTRP6升高与GDM相关,是GDM的独立危险因素。

妊娠期糖尿病患者血清Xenin-25、CTRP12水平及对妊娠结局的影响

目的分析妊娠期糖尿病(GDM)患者血清神经降压素相关肽(Xenin-25)、C1q肿瘤坏死因子相关蛋白12(CTRP12)与妊娠结局的关系。方法选取2021年2月—2022年2月川北医学院附属医院生殖医学科诊治的GDM患者92例为GDM组,再根据是否发生不良妊娠结局,分为预后不良亚组(n=34)和预后良好亚组(n=58)。以同期健康妊娠妇女50例为正常妊娠组。采用酶联免疫吸附法检测血清Xenin-25、CTRP12水平;Pearson相关性分析血清Xenin-25、CTRP12与糖代谢指标的相关性;多因素Logistic回归分析影响GDM患者不良妊娠结局的因素;受试者工作特征曲线评价血清Xenin-25、CTRP12对妊娠结局的预测价值。结果GDM组血清Xenin-25、CTRP12低于正常妊娠组,而空腹血糖(FPG)、糖化血红蛋白(HbA_(1c))、空腹胰岛素(FINS)及稳态模型评估的胰岛素抵抗指数(HOMA-IR)水平均高于正常妊娠组(t/P=16.046/<0.001,22.114/<0.001,11.510/<0.001,13.666/<0.001,12.101/<0.001,14.413/<0.001);GDM组血清Xenin-25、CTRP12表达与FPG、FINS、HbA_(1c)及HOMA-IR呈显著负相关(Xenin-25:r/P=-0.665/<0.001,-0.598/<0.001,-0.567/<0.001,-0.702/<0.001;CTRP12:r/P=-0.579/<0.001,-0.622/<0.001,-0.667/<0.001,-0.725/<0.001);预后不良亚组血清Xenin-25、CTRP12低于预后良好亚组,HOMA-IR高于预后良好亚组(t/P=6.783/<0.001,17.997/<0.001,15.146/<0.001);血清CTRP12升高、Xenin-25升高是影响GDM患者不良妊娠结局的独立保护因素[OR(95%CI)=0.646(0.499~0.837),0.619(0.465~0.824)],HOMA-IR升高是危险因素[OR(95%CI)=1.353(1.110~1.649)]。血清Xenin-25、CTRP12及二者联合预测GDM患者不良妊娠结局的AUC分别为0.828、0.815、0.870,二者联合优于各自单独预测效能(Z=4.113、4.327,P=0.003、0.001)。结论GDM孕妇血清Xenin-25、CTRP12水平降低,均参与GDM的疾病过程,二者联合对GDM患者不良妊娠结局具有较高的评估价值。

GDM患者产后抑郁现状调查及影响因素分析

目的:调查妊娠期糖尿病(GDM)患者产后抑郁(PPD)发生现状并分析影响因素。方法:选择2021年6月-2023年8月在本院就诊的GDM患者274例,产后6周评估其PPD发生情况并分成PPD组和对照组。采用《GDM患者调查问卷》收集两组21项资料并予以比较,并通过多因素分析筛查PPD的相关因素。结果:本研究共筛查出PPD 59例(21.5%)。PPD组与对照组夫妻关系、人格类型、新生儿性别符合期待、新生儿疾病、产后糖尿病、产后睡眠障碍等发生存在差异(P<0.05);夫妻关系差(OR=2.249,95%CI 1.213~4.170)、易感性人格(OR=3.219,95%CI 1.771~5.853)、新生儿性别不符合期待(OR=2.098,95%CI 1.118~3.936)、产后糖尿病(OR=2.517,95%CI 1.376~4.603)和产后睡眠障碍(OR=2.846,95%CI 1.609~5.034)为GDM患者发生PPD的危险因素。结论:夫妻关系差、易感性人格、新生儿性别不符合期待、产后遗留糖尿病、产后睡眠障碍与GDM患者发生PPD有关,应加强对上述特征人群的心理关注,及时开展精准干预,以防控PPD的发生。