Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, is enriched in exosomes derived from platelet-rich plasma (PRP-Exos). However, the potential role of PRP-Exos-S1P in diabetic wound healing remains unclear. In this study, we investigated the underlying mechanism of PRP-Exos-S1P in diabetic angiogenesis and wound repair. Exosomes were isolated from PRP by ultracentrifugation and analysed by transmission electron microscopy, nanoparticle tracking analysis and western blotting. The concentration of S1P derived from PRP-Exos was measured by enzyme-linked immunosorbent assay. The expression level of S1P receptor1–3 (S1PR1–3) in diabetic skin was analysed by Q-PCR. Bioinformatics analysis and proteomic sequencing were conducted to explore the possible signalling pathway mediated by PRP-Exos-S1P. A diabetic mouse model was used to evaluate the effect of PRP-Exos on wound healing. Immunofluorescence for cluster of differentiation 31 (CD31) was used to assess angiogenesis in a diabetic wound model. In vitro, PRP-Exos significantly promoted cell proliferation, migration and tube formation. Furthermore, PRP-Exos accelerated the process of diabetic angiogenesis and wound closure in vivo. S1P derived from PRP-Exos was present at a high level, and S1PR1 expression was significantly elevated compared with S1PR2 and S1PR3 in the skin of diabetic patients and animals. However, cell migration and tube formation were not promoted by PRP-Exos-S1P in human umbilical vein endothelial cells treated with shS1PR1. In the diabetic mouse model, inhibition of S1PR1 expression at wounding sites decreased the formation of new blood vessels and delayed the process of wound closure. Bioinformatics analysis and proteomics indicated that fibronectin 1 (FN1) was closely related to S1PR1 due to its colocalization in the endothelial cells of human skin. Further study supported that FN1 plays an important role in the PRP-Exos-S1P-mediated S1PR1/protein kinase B signalling pathway. PRP-Exos-S1P promotes angiogenesis in diabetic wound healing via the S1PR1/protein kinase B/FN1 signalling pathway. Our findings provide a preliminary theoretical foundation for the treatment of diabetic foot ulcers using PRP-Exos in the future.

Objective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood. Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups. Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p< 0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p< 0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p< 0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p< 0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p< 0.05). Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs. Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.

Few studies have examined the effect of rTMS on impaired emotional processing in apathetic Parkinson's disease (PD) patients, which impelled us to use a combination of repetitive transcranial magnetic stimulation (rTMS) with event-related potentials (ERPs) to gain insight into the underlying mechanisms. Apathetic and non-apathetic patients diagnosed with PD performed a facial emotion categorization task, and ERP data were collected before and after HF-rTMS or sham stimulation over the right dorsolateral prefrontal cortex (DLPFC). We observed the behavioural results and early components of P100 and N170. After rTMS, accuracy (ACC) was higher for negative expressions, and reaction times (RTs) were shorter for all expressions in both apathetic and non-apathetic patients. P100 amplitudes significantly increased except for negative expressions in the right hemisphere, and hemisphere lateralization was reversed in apathetic patients. P100 amplitudes increased for all expressions bilaterally in non-apathetic patients. N170 amplitudes in apathetic patients increased, and hemisphere lateralization was normalized. Neither the apathetic sham group nor the non-apathetic cohort of patients showed changes in P100 or N170 lateralization. The effects of rTMS on PD patients relative to normal subjects should be compared and observed over a long period of time. HF-rTMS over the right DLPFC is beneficial for emotional processing in both apathetic and non-apathetic PD patients but shows different sensitivities. The effect of rTMS on emotional processing impairments in apathetic PD patients is profound. Treatment with rTMS may be an important, novel nonpharmaceutical approach for apathy in PD patients.

This study aimed to investigate the cerebral blood flow (CBF) and frontal lobe cognitive function in severe internal carotid artery (ICA) stenosis patients with different types of collateral circulation. One hundred twenty-six patients with severe unilateral ICA stenosis were enrolled. Digital subtraction angiography (DSA) was performed to recruit patients with one of three common types of collateral circulation: anterior communicating artery (AcoA), posterior communicating artery (PcoA) and ophthalmic artery (OA). The hemodynamic parameters of the middle cerebral artery (MCA) were measured using transcranial Doppler (TCD), and the individual frontal lobe cognitive attention functions were evaluated using Word Fluency Test, Trail-Making Test (TMT), Digit Span, and Stroop Color Word Test (SCWT). The correlation between hemodynamic changes and the scores of all tasks was analyzed. On the side of arterial stenosis, the CBF velocities were highest in AcoA group and lowest in the OA group. All patients performed worse in TMT and Digit Span than the matched normal controls. The AcoA group exhibited a lower pulsatility index (PI) and a longer response time in the Stroop task, but had a higher accuracy rate in the Stroop task and higher scores in Word Fluency Test than the PcoA and OA groups. In all the three groups, PI was positively correlated with the accuracy rate for Stroop interference effects. Our findings suggested that the frontal lobe cognitive function of patients with ICA was impaired, and AcoA collaterals may be beneficial for selective attention functions, whereas OA collaterals may be associated with impairment of selective attention functions. Additionally, a high PI may be an indicator for identifying impaired selective attention in patients with severe ICA stenosis.

Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients’ quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients’ physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence.

Aim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population. Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed. Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p< 0.05) but lower blood uric acid (UA) (p< 0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p< 0.05) but presented with lower UA (p< 0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p< 0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH. Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.