This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Prescriptions ; Drug Combinations ; Diabetic Angiopathies/drug therapy* ; Data Mining ; Diabetes Mellitus/drug therapy*

OBJECTIVE: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated. RESULTS: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). CONCLUSION CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.
Alkaloids ; pharmacology ; Animals ; Apoptosis ; drug effects ; Atherosclerosis ; Diabetes Mellitus, Experimental ; Diabetic Angiopathies ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Male ; Ophiopogon ; chemistry ; Panax notoginseng ; chemistry ; Polysaccharides ; pharmacology ; Rabbits ; Saponins ; pharmacology

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.
Diabetes Complications ; Diabetic Angiopathies* ; Glucose ; Glycosylation End Products, Advanced* ; Humans ; Hyperglycemia ; Risk Factors

BACKGROUND: Microvascular complications in type 2 diabetes (T2DM), including diabatic retinopathy (DR), diabetic kidney disease (DKD), diabetic peripheral neuropathy (DPN) are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine (CM) has been widely used for treating diabetic mellitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. OBJECTIVE: To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. METHODS: This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups: DR study group (32 cases) and a corresponding control group (32 cases), DR+DKD study group (64 cases) and a corresponding control group (64 cases), DR+DPN study group (64 cases) and a corresponding control group (64 cases), DR+DKD+DPN study group (56 cases) and a corresponding control group (56 cases). The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. CONCLUSION This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. (Registration No. ChiCTR-IPR-15007072).
Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Diabetic Angiopathies ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Outcome Assessment (Health Care) ; Randomized Controlled Trials as Topic

PURPOSE: The purpose of this study was to understand the situation of diabetes patients receiving examinations for diabetes complications and to explore the factors influencing their intention to receive examinations for diabetes complications. METHODS: A cross-sectional study was performed that included 251 diabetes patients who visited outpatient clinics in Southern Taiwan. A survey using a self-administered questionnaire was conducted from October 2015 to January 2016. The questionnaire included items on demographic characteristics, perceived susceptibility to diabetes complications, perceived seriousness of diabetes complications, perceived benefits of taking action to receive diabetes complication examinations, perceived barriers to taking action to receive diabetes complication examinations, and the intention to receive diabetes complication examinations. The data were analyzed using regression analysis. RESULTS: The percentage of participants who received fundus, foot, and kidney examinations was 67.7%, 61.4%, and 73.3%, respectively. Every point increase on the perceived barriers to taking action to receive diabetes complication examinations scale increased the intention to receive a foot examination in the following year by 0.91 times (p = .002), and every point increase on the perceived susceptibility to diabetes complications scale increased the intention to receive a kidney examination in the following year by 1.19 times (p = .045). CONCLUSIONS: Nurses should shoulder the responsibility to increase patients' intention to receive examination of diabetes complications. The results of this study can be used to promote nurses' care efficacy in preventing diabetes complications. They can also provide medical institutions with information to establish prevention and control policies for diabetes complications.
Ambulatory Care/utilization ; Cross-Sectional Studies ; Diabetic Angiopathies/nursing/*prevention & control/psychology ; Diabetic Nephropathies/nursing/*prevention & control/psychology ; Disease Susceptibility/psychology ; Early Diagnosis ; Female ; Humans ; Intention ; Kidney Function Tests ; Male ; Middle Aged ; Nurse-Patient Relations ; Ophthalmoscopy ; Patient Acceptance of Health Care/*psychology ; Perception ; Physical Examination/nursing/*psychology/utilization ; Taiwan

PURPOSE: To investigate the clinical and morphological characteristics in relation to risk of bifurcation intracranial aneurysm rupture. MATERIALS AND METHODS: Data from 202 consecutive patients with 219 bifurcation aneurysms (129 ruptured and 90 unruptured) managed at the authors' facility between August 2011 and July 2014 were retrospectively reviewed. Based on their clinical records and CT angiographic findings, the ability of risk factors to predict aneurysm rupture was assessed using statistical methods. RESULTS: Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were negatively correlated with aneurysm rupture. Aneurysms located in the middle cerebral artery, daughter artery ratio, lateral angle ratio (LA ratio), and neck width were negatively correlated with rupture. Aneurysms located in the anterior communicating artery, irregularity, with daughter sac, depth, width, maximum size, aspect ratio (AR), depth-to-width ratio, and bottleneck factor were significantly and positively correlated with rupture. Binary logistic regression model revealed that irregular shape [odds ratio (OR) 6.598] and AR (OR 3.507) strongly increased the risk of bifurcation aneurysm rupture, while age (OR 0.434), cerebral atherosclerosis (OR 0.125), neck width (OR 0.771), and LA ratio (OR 0.267) were negatively correlated with rupture (p<0.05). Receiver operating characteristic analysis revealed the threshold values of AR and LA ratio to be 1.18 and 1.50, respectively. CONCLUSION: Age (≥60 yr), cerebral atherosclerosis, and aneurysms with a larger neck width and larger LA ratio are protective factors against bifurcation aneurysm rupture. An aneurysm with an irregular shape and an increased AR reflect the greater likelihood of a rupture.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aneurysm, Ruptured/*diagnostic imaging ; Cerebral Angiography/*methods ; *Computed Tomography Angiography ; Developmental Disabilities ; Diabetic Angiopathies/complications ; Female ; Humans ; Hypertension/complications ; Intracranial Aneurysm/*diagnostic imaging ; Intracranial Arteriosclerosis/complications ; Logistic Models ; Male ; Middle Aged ; Middle Cerebral Artery/diagnostic imaging ; Odds Ratio ; Protective Factors ; ROC Curve ; Retrospective Studies ; Risk Factors

OBJECTIVE: To investigate the impact of vascular factors on the electrophysiologic severity of diabetic neuropathy (DPN). METHODS: Total 530 patients with type 2 diabetes were enrolled retrospectively. We rated severity of DPN from 1 (normal) to 4 (severe) based on electrophysiologic findings. We collected the data concerning vascular factors (including brachial-ankle pulse wave velocity [PWV], ankle brachial index, ultrasound of carotid artery, lipid profile from the blood test, and microalbuminuria [MU] within 24 hours urine), and metabolic factors of diabetes (such as glycated hemoglobin [HbA1c]). We analyzed the differences among the four subgroups using χ2 test and ANOVA, and ordinal logistic regression analysis was performed to investigate the relationship between significant variables and severity of DPN. RESULTS: The severity of DPN was significantly associated with duration of diabetes, HbA1c, existence of diabetic retinopathy and nephropathy, PWV, presence of plaque, low density lipoprotein-cholesterol and MU (p<0.05). Among these variables, HbA1c and presence of plaque were more significantly related with severity of DPN in logistic regression analysis (p<0.001), and presence of plaque showed the highest odds ratio (OR=2.52). CONCLUSION: Our results suggest that markers for vascular wall properties, such as PWV and presence of plaque, are significantly associated with the severity of DPN. The presence of plaque was more strongly associated with the severity of DPN than other variables.
Ankle Brachial Index ; Carotid Arteries ; Carotid Stenosis ; Diabetic Angiopathies ; Diabetic Neuropathies* ; Diabetic Retinopathy ; Electromyography ; Hematologic Tests ; Hemoglobin A, Glycosylated ; Humans ; Logistic Models ; Odds Ratio ; Pulse Wave Analysis ; Retrospective Studies ; Ultrasonography

PURPOSE: To validate the Cardiff Wound Impact Schedule (CWIS) to assess the health-related quality of life (HRQoL) of Sri Lankan patients with diabetic leg and foot ulcers. METHODS: English version of CWIS was examined for cultural compatibility, translated into Sinhala and pretested. The Sinhala versionwas administered in parallel with the validated Sinhala version of SF-36 by an interviewer to all patients (n = 140) at baseline to determine the construct validity. Reliability of CWIS was measured by internal consistency and test-retest stability. The instrument was readministered in 2 weeks on 33 patients with nonhealing ulcers to determine the test-retest stability and in 3 months on 50 patients with healed ulcers to determine the ability of CWIS to discriminate HRQoL between patients with healed versus nonhealed ulcers. Acceptability of CWIS was assessed by the response rate, completion rate and the average time taken to complete a single interview. RESULTS: The construct validity demonstrated moderately significant correlations between related subscales of CWIS and SF-36 (Spearman's r = .32–.51, p = .021 to p < .001) for the whole study sample. Internal consistencies (Cronbach α = .68–.86) and test-retest stability (.56–.70) were acceptable. The tool was sensitive in discriminating the impact of the wound on HRQoL in healed versus nonhealed status (p ≤ .001). The tool showed good acceptability. CONCLUSIONS: The Sinhala version of CWIS is valid, reliable and acceptable for assessing the impact of wound on HRQoL. This instrument is sensitive in detecting the differences of the impact of healed and nonhealed ulcers on QoL in patients with diabetic leg and foot ulcer.
Adult ; Aged ; Cross-Cultural Comparison ; Cross-Sectional Studies ; Diabetic Angiopathies/*diagnosis/ethnology ; Diabetic Foot/diagnosis/ethnology ; Female ; Humans ; Leg Ulcer/*diagnosis/ethnology ; Male ; Middle Aged ; Quality of Life ; Reproducibility of Results ; Severity of Illness Index ; Sri Lanka/ethnology ; Surveys and Questionnaires

Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL.
Atherosclerosis ; Diabetes Mellitus ; Diabetic Angiopathies ; Endothelial Cells* ; Fatty Acids, Nonesterified ; Glucose* ; Human Umbilical Vein Endothelial Cells ; Humans* ; Hyperglycemia ; Reactive Oxygen Species ; RNA, Small Interfering ; Transfection

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.
Animals ; Diabetes Mellitus, Experimental ; complications ; metabolism ; Diabetic Angiopathies ; genetics ; metabolism ; Diet ; adverse effects ; Glycation End Products, Advanced ; metabolism ; Humans ; Interleukin-6 ; metabolism ; Kidney ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Pancreas ; metabolism ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; genetics ; metabolism ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism