Coagulation Function and Type 2 Diabetic Kidney Disease: A Real-World Observational Study.

Objectives: Type 2 diabetic kidney disease (DKD), a chronic microvascular complication of diabetes, may exhibit a complex interrelation with coagulation function. This study is aimed at elucidating the association between coagulation function and DKD. Methods: This was a real-world observational study conducted in Beijing, involving 2,703 participants. All patients with diabetes were classified into two groups, viz., DKD and non-DKD groups. Effect magnitudes are denoted as odds ratios (OR) with a 95% confidence interval (CI). To mitigate potential bias in group comparisons, we employed propensity score matching (PSM). Results: After adjusting for variables such as age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), triglyceride (TG), c-reactive protein (CRP), platelet (PLT), and serum albumin (sALB), it was discerned that fibrinogen (FIB) (OR, 95% CI, P: 1.565, 1.289-1.901, <0.001) and fibrinogen degradation products (FDP) (1.203, 1.077-1.344, 0.001) were significantly correlated with an increased risk of DKD. To facilitate clinical applications, a nomogram prediction model was established, demonstrating commendable accuracy for DKD prediction. Conclusions: Our findings suggest that elevated levels of FIB and FDP serve as potential risk indicators for DKD, and coagulation function may play an important role in the occurrence and development of DKD.

Association between serum complements and kidney function in patients with diabetic kidney disease.

Objective: We aimed to explore the association between serum complements and kidney function of diabetic kidney disease (DKD) in Chinese patients. Methods: This is a retrospective study involving 2,441 participants. DKD was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) categories. Participants were classified as stages G1-G5 by KDIGO glomerular filtration rate (GFR) categories. Effect sizes are expressed as odds ratio (OR) with 95% confidence interval (CI). Results: After balancing age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1C), serum triglyceride (TG), and urinary albumin-to-creatinine ratio (UACR) between the G2-G5 and control groups, per 0.1 g/L increment in serum complement C3 was significantly associated with a 27.8% reduced risk of DKD at G5 stage (OR, 95% CI, P: 0.722, 0.616-0.847, <0.001) relative to the G1 stage. Conversely, per 0.1 g/L increment in serum complement C4 was associated with an 83.0-177.6% increased risk of G2-G5 stage (P<0.001). Serum complement C1q was not statistically significant compared to controls at all stages prior to or after propensity score matching. Conclusions: Our results indicate that high concentrations of serum C4 were associated with the significantly elevated risk of kidney function deterioration across all stages, and reduced serum C3 levels with an increased risk of DKD stage G5.

Application Study of Brain Structure and Functional Magnetic Resonance Imaging in Patients with Systemic Lupus Erythematosus and Cognitive Dysfunction.

Objective: This study was aimed to investigate the application value of brain magnetic resonance imaging (MRI) technique, including arterial spin labeling (ASL) and diffusion tensor imaging (DTI) in patients with systemic lupus erythematosus (SLE) and cognitive dysfunction (CDF). Methods: A total of 50 patients with SLE admitted to the hospital from September 2020 to December 2022 were selected and divided into the group with CDF (n = 21) and the group without CDF (n = 29) according to the score of Montreal Cognitive Assessment Scale (MoCA). Additionally, 10 healthy individuals who underwent physical examinations during the same period were recruited as controls. After the conventional MRI, DTI and ASL data of all subjects were collected, statistical parametric mapping software combined with voxel morphology is applied for gray matter volume, white matter and gray matter cerebral blood flow (CBF) analysis among different groups. Results: There is a statistically significant difference in conventional MRI findings between the SLE group and the control group (P < .05). However, There was no significant difference in white matter fractional anisotropy (FA) values between the two groups (P > .05). The apparent diffusion coefficients (ADC) of the right precuneus and the right Brodmann's area 21 and 6 in SLE patients with CDF were significantly higher than SLE patients without CDF (P < .05). In comparison to the non-CDF group, the CDF group exhibited reduced gray matter volume, primarily in the anterior cingulate gyrus, left frontal lobe, and right insula (P < .05). Meanwhile, the white matter and gray matter cerebral blood flow (CBF) of SLE patients with CDF were significantly lower than those without CDF. (P < .05). Correlation analysis showed that the MoCA score was positively associated with the volume of gray matter in the right insula, bilateral frontal lobe, left temporal lobe, and cingulate gyrus (P < .05). Additionally, MoCA score was also found to be positively associated with the CBF of white matter and gray matter (P < .05). Conclusions: Alterations in gray matter volume and CBF in SLE patients are closely associated with combined CDF and can be observed by DTI and ASL techniques.

Rapamycin alleviates cognitive impairment in murine vascular dementia: The enhancement of mitophagy by PI3K/AKT/mTOR axis.

There are no approved symptomatic treatments for vascular dementia (VaD). Rapamycin (RAPA) improves cognitive deficits in Alzheimer's disease rats. To explore whether RAPA improves cognitive impairment after VaD and its possible molecular mechanisms. Thirty Sprague Dawley rats were randomly divided into three groups: sham (received sham-operation), VaD model (received permanent ligation of bilateral carotid arteries) and RAPA (7.5 mg/kg) treatment. Cognitive function was evaluated by Morris water maze test. Neuronal apoptosis was evaluated by TUNEL staining. Mitophagy was assessed by mitochondrial DNA (mtDNA), ATP level, transmission electron microscope and mitophagy-associated proteins. Proteins were quantified by Western blot and immunofluorescence. BV2 cells were exposed to RAPA or/and MHY1485 (mTOR activator) to verify in vivo results. Compared to VaD rats, the escape latency of RAPA-treated rats was significantly decreased, and time spent in target quadrant was longer. Pathologic changes, mitochondrial dysfunction, increase of neuronal apoptosis and related proteins in VaD rats were remarkably alleviated by RAPA. After RAPA treatment, an increase in number of autophagosomes was observed, along with up-regulation of mitophagy-related proteins. Overexpression of PI3K, AKT and mTOR were suppressed by RAPA treatment. In vitro experiments confirmed effects of RAPA, and demonstrated that MHY1485 addition reversed the RAPA-caused apoptosis inhibition and mitophagy enhancement. Overall, RAPA improved the cognitive impairment of VaD rats, alleviated neuronal injury and mitochondrial dysfunction. We proposed a potential mechanism that RAPA may play improving role by inhibiting neuronal apoptosis and enhancing mitophagy through PI3K/AKT/mTOR pathway. Findings provided an exciting possibility for novel treatment strategy of VaD.

Anti-cyclic citrullinated peptide antibody predicts the development of rheumatoid arthritis in patients with undifferentiated arthritis.

BACKGROUND: Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development. METHODS: We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression. RESULTS: A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibody-positivity (66.7% vs. 10.7%, χ = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017, 95% confidence interval: 5.803-55.938; P < 0.001). CONCLUSION: As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

DL-3-n-butylphthalide alleviates vascular cognitive impairment by regulating endoplasmic reticulum stress and the Shh/Ptch1 signaling-pathway in rats.

BACKGROUND: DL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers. METHODS: Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30 mg/kg), NBP 60 (60 mg/kg), and NBP 120 (120 mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation. RESULTS: NBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real-time quantitative polymerase chain reaction analysis revealed that plasticity-related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS-related markers decreased. CONCLUSION: The results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.

Cognitive Function and Prognosis of Multimodal Neuroimage-Guided Thrombectomy on Mild to Moderate Anterior Circulation Infarction Patients with Broadened Therapeutic Window: A Prospective Study.

BACKGROUND AND OBJECTIVES: Endovascular mechanical thrombectomy is an important approach for acute ischemic stroke (AIS) treatment. Multimodal neuroimaging methods ideally provide the exact localization, extent, and metabolic activity of target tissues. Post-stroke cognitive impairment has recently been realized to be another major concern except for neurological function impairment. The aim of our study was to carry out a prospective study to compare neurological and cognitive functions after thrombectomy in mild to moderate anterior circulation infarction patients selected by multimodal neuroimaging. METHODS: Ninety patients were recruited from January 2016 to March 2017 consecutively. Neurological function was assessed by NIHSS before thrombectomy, and 6 h, 24 h, 7 days, 90 days after mechanical thrombectomy. Cognitive functions were evaluated by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Hachinski Ischemic Scale. RESULTS: Patients who received mechanical thrombectomy had significantly better neurological functions at 6 h (p < 0.001), 24 h (p < 0.001), 7 days (p < 0.001), and 90 days (p < 0.001), as well as cognitive functions evaluated by MoCA (26.23 ± 3.85 vs. 24.62 ± 2.25, p = 0.022, n = 85) and MMSE (26.65 ± 2.77 vs. 25.10 ± 2.36, p = 0.023, n = 85) compared to the standard therapy group. CONCLUSIONS: The current prospective study demonstrated that mechanical thrombectomy can significantly improve neurological and cognitive functions in patients with mild to moderate AIS at broadened therapeutic window under multimodal CT and multimodal MRI imaging.

Application of high frequency color Doppler ultrasound in the monitoring of rheumatoid arthritis treatment.

The aim of the present study was to explore the use of high frequency color Doppler ultrasound to measure synovial thickness and blood flow to assess the therapeutic value of the recombinant human tumor necrosis factor (TNF) II receptor antibody fusion protein in rheumatoid arthritis (RA) treatment. A total of 36 clinically-diagnosed patients with RA were treated with methotrexate tablets or the recombinant TNF-receptor antibody fusion protein for 24 weeks. Joint synovial thickness and synovial blood flow integrity were monitored by high frequency color Doppler in the second metacarpophalangeal joint in one hand. The correlation of the erythrocyte sedimentation rate, C-reactive protein (CRP) and 28-joint disease activity score (DAS28) with the ultrasound parameters were analyzed. Metacarpophalangeal second joint 2 (MCP2) synovial thickness, wrist joint synovial thickness and MCP2 synovial blood flow, prior and subsequent to the treatment, have a high correlation with DAS28 (P<0.05), and the MCP2 synovial blood flow integral has a strong correlation with CRP. Evaluating the wrist joint synovial thickness and synovial integrity of the second metacarpophalangeal joint using high frequency ultrasound detection can effectively evaluate the disease status in patients with RA. This procedure is potentially valuable as a means of evaluating the curative effects of RA treatments.