An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.

Spontaneous rupture­induced life­threatening mediastinal mixed germ cell tumor: A case report and therapeutic considerations.

Spontaneous rupture and hemorrhage of mediastinal germ cell tumors is a rare occurrence. In the current report, the case of a 20-year-old male patient who was admitted with chest tightness and dyspnea is presented. An urgent chest CT scan revealed a large tumor in the right anterior mediastinum, measuring ~12 cm in diameter, with associated intratumoral hemorrhage. An emergency thoracotomy was performed to excise the lesion, which revealed that the bleeding was caused by a ruptured tumor. Postoperative pathological findings revealed a mediastinal mixed germ cell tumor consisting of four pathological types: Embryonal carcinoma, seminoma, yolk sac tumor and immature teratoma. Postoperatively, the patient showed marked improvement in the symptoms of dyspnea. However, the follow-up outcome was poor, and the patient succumbed 2 months after surgery. To the best of our knowledge, there are no reports of rupture and hemorrhage involving >4 mixed germ cell tumors. In the present report, the experience of the treatment of the patient is summarized, and literature was reviewed to improve clinicians' awareness of the disease.

External validation of the SYNTAX score II 2020 in patients with chronic renal insufficiency.

BACKGROUND: The SYNTAX score Ⅱ 2020 (SSⅡ-2020) was created as a customized decision-making tool for individuals diagnosed with complex coronary artery disease (CAD). Nevertheless, there has been a scarcity of research investigating the long-term predictive significance of SSⅡ-2020 for patients with both CAD and chronic renal insufficiency (CRI) who undergo percutaneous coronary intervention (PCI). AIMS: We sought to showcase the prognostic capacity of SSII-2020 in evaluating long-term all-cause mortality (ACM) within this high-risk patient cohort. METHODS: A retrospective cohort comprising 1156 individuals diagnosed with CRI and exhibiting left main CAD, three-vessel CAD or both was included in this investigation. We categorized participants into three groups based on the optimal SSII-2020 threshold for predicting long-term ACM, determined using the X-tile software. RESULTS: At the median follow-up duration of 6.3 years, the ACM rates were determined to be 10% in the low, 17% in the moderate, and 28% in the high SSII-2020 groups (p < 0.001). Employing multivariate Cox regression analysis, it was observed that the high SSII-2020 group exhibited a 3.289-fold increased risk of ACM (95% confidence interval [CI]: 2.229-4.856, p < 0.001) compared with the low SSII-2020 group, whereas the high SSII-2020 group displayed a 1.757-fold (95% CI: 1.190-2.597, p = 0.005) in comparison to the median SSII-2020 groups. Compared with SSII, the SSII-2020 had an incremental value for predicting 7-year ACM (C-index: 0.662 vs. 0.534, p = 0.007; IDI: 0.016, p < 0.001). CONCLUSIONS: SSII-2020 enhances long-term ACM prediction, facilitates improved risk stratification, and improves clinical utility for PCI patients with complex CAD and CRI.

Expert consensus on the relevance of intestinal microecology and hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) affects gut microbial homeostasis, and intestinal microecology (IM) may also affect the prognosis of HSCT through multiple mechanisms. In order to further understand the key issues of the correlation between intestinal microecology and HSCT and to learn and absorb new research progress, the Tumor and Microecology Committee of China Anti-Cancer Association organized relevant experts to discuss together and propose the "Expert Consensus on the Relevance of Intestinal Microecology and Hematopoietic Stem Cell Transplantation" for clinicians' reference in their practical work. It is a reference for clinicians in practice and provides a basis for further in-depth research in the field of tumor and microecology.

Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78.

Colorectal cancer is one of the most common malignancies worldwide. Although initially effective, patients who receive chemotherapy ultimately experience various complications and develop chemo-resistance, leading to cancer recurrence. Therefore, we aimed to find a drug with good efficacy and low toxicity that could enhance the treatment with 5-Fluorouracil (a commonly used clinical drug) and reduce its dosing. Corilagin, an anti-tumor natural product, has received widespread attention. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal cancer cells and plays a key role in the proliferation, migration and drug resistance of cancer cells. Importantly, GRP78 can affect the apoptosis induced by 5-fluorouracil in CRC cells. In the present study, we determined the synergistic anti-tumor activity of the combination treatment by cell proliferation assay, apoptosis assay, fluorescent staining, cell cycle analysis, WB and PCR assays. This synergistic effect was associated with S-phase blockade, intracellular reactive oxygen species production and downregulation of GRP78. Taken together, our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.

Oral Pathogenic Bacteria and the Oral-Gut-Liver Axis: A New Understanding of Chronic Liver Diseases.

Liver diseases have long been a prevalent cause of morbidity and mortality, and their development and progression involve multiple vital organs throughout the body. Recent studies on the oral-gut-liver axis have revealed that the oral microbiota is associated with the pathophysiology of chronic liver diseases. Since interventions aimed at regulating oral biological disorders may delay the progress of liver disease, it is crucial to better comprehend this process. Oral bacteria with potential pathogenicity have been extensively studied and are closely related to several types of chronic liver diseases. Therefore, this review will systemically describe the emerging role of oral pathogenic bacteria in common liver diseases, including alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, autoimmune liver diseases (AILD), and liver cancer, and bring in new perspectives for future research.

Cognitive Behavioral Therapy for AIDS Prevention among College Students in China: A Cluster Randomized Controlled Trial.

BACKGROUND: Acquired immune deficiency syndrome (AIDS) is a serious worldwide public health problem and has become the focus of prevention and control in China, while the student population is the key population for AIDS prevention. OBJECTIVE: The purpose of this study was to investigate the effects of cognitive behavioral therapy (CBT) on college students' AIDS-related cognitions, attitudes, and behaviors, and to find programmatic strategies for AIDS prevention in terms of changing college students' cognitions and behaviors. METHODS: In a cluster randomized controlled trial, 233 undergraduate students were assigned to the CBT group (CBT-based intervention, n=92), the TAU group (treatment as usual, n=72), and the CON group (no intervention, n=59). AIDS-related knowledge, attitudes, and behaviors of participants were assessed at pre-intervention, post-intervention, and follow-up. RESULTS: After one month of the study, AIDS-related knowledge, attitudes, and behaviors improved in both the TAU and CBT groups, while there were no significant changes in the CON group. The intervention effect was more significant and sustainable in the CBT group compared to the TAU group. CONCLUSIONS: The application of CBT in AIDS prevention among college students is feasible, acceptable, and effective. CBT can increase the level of knowledge about AIDS, improve AIDS-related attitudes, and increase willingness to use condoms. CBT is expected to replace traditional health education as an innovative tool for AIDS prevention because of its long-lasting and efficacious nature.

Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis.

The interaction between intestinal microecological dysregulation, altered inflammatory factors, and cirrhosis is unclear. The aim of this systematic review and meta-analysis was to synthesize the results of previous studies to assess the efficacy of probiotics in the treatment of cirrhosis and their effect on inflammatory factors, as well as to explore the relationship between gut microecological dysregulation and liver disease to gain a deeper understanding of this interaction. Up to December 2022, eligible studies were identified by searching the following databases: National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, Embase, Medline, and the Cochrane Library. Statistical analysis was performed using software RevMan Version 5.4. A total of 33 eligible randomized controlled trials were included in the study, and data on probiotic strains, duration of intervention, measures in the control group, and outcomes were extracted and evaluated. Compared to the control group, the experimental group had significant improvements in overall efficacy. The results of the meta-analysis revealed that probiotic use significantly decreased biochemical parameters for liver function, including aspartate transaminase, alanine aminotransferase, and total bilirubin. Similar result was obtained in interleukin-6, tumor necrosis factor-α, and endotoxin. However, probiotic intervention did not significantly affect interleukin-2 and interleukin-10. The current meta-analysis illustrates that probiotic supplementation reduces inflammatory markers and biochemical parameters for liver function in patients with cirrhosis, suggesting that probiotic management may be a novel treatment for cirrhosis. Furthermore, the interaction of the gut microbiota, associated metabolites, and inflammation factors with cirrhosis may provide a promising therapeutic target for the pharmacological and clinical treatment of cirrhosis.

Nanodroplet-Based Super-Resolution Ultrasound Localization Microscopy.

Over the past decade, super-resolution ultrasound localization microscopy (SR-ULM) has revolutionized ultrasound imaging with its capability to resolve the microvascular structures below the ultrasound diffraction limit. The introduction of this imaging technique enables the visualization, quantification, and characterization of tissue microvasculature. The early implementations of SR-ULM utilize microbubbles (MBs) that require a long image acquisition time due to the requirement of capturing sparsely isolated microbubble signals. The next-generation SR-ULM employs nanodroplets that have the potential to significantly reduce the image acquisition time without sacrificing the resolution. This review discusses various nanodroplet-based ultrasound localization microscopy techniques and their corresponding imaging mechanisms. A summary is given on the preclinical applications of SR-ULM with nanodroplets, and the challenges in the clinical translation of nanodroplet-based SR-ULM are presented while discussing the future perspectives. In conclusion, ultrasound localization microscopy is a promising microvasculature imaging technology that can provide new diagnostic and prognostic information for a wide range of pathologies, such as cancer, heart conditions, and autoimmune diseases, and enable personalized treatment monitoring at a microlevel.

Clinical and cognitive correlates tractography analysis in patients with white matter hyperintensity of vascular origin.

Purpose: White matter hyperintensity lesions (WMHL) in the brain are a consequence of cerebral small vessel disease and microstructural damage. Patients with WMHL have diverse clinical features, and hypertension, advanced age, obesity, and cognitive decline are often observed. However, whether these clinical features are linked to interrupted structural connectivity in the brain requires further investigation. This study therefore explores the white matter pathways associated with WMHL, with the objective of identifying neural correlates for clinical features in patients with WMHL. Methods: Diffusion magnetic resonance imaging (MRI) and several clinical features (MoCA scores, hypertension scores, body mass index (BMI), duration of hypertension, total white matter lesion loads, and education.) highly related to WMHL were obtained in 16 patients with WMHL and 20 health controls. We used diffusion MRI connectometry to explore the relationship between clinical features and specific white matter tracts using DSI software. Results: The results showed that the anterior splenium of the corpus callosum, the inferior longitudinal fasciculus, the anterior corpus callosum and the middle cerebellar peduncle were significantly correlated with hypertension scores (false discovery rate (FDR) = 0.044). The anterior splenium of the corpus callosum, the left thalamoparietal tract, the inferior longitudinal fasciculus, and the left cerebellar were significantly correlated with MoCA scores (FDR = 0.016). The anterior splenium of corpus callosum, inferior fronto-occipital fasciculus, cingulum fasciculus, and fornix/fimbria were significantly correlated with body mass index (FDR = 0.001). Conclusion: Our findings show that hypertension score, MoCA score, and BMI are important clinical features in patients with WMHL, hypertension degree and higher BMI are associated with whiter matter local disconnection in patients with WMHL, and may contribute to understanding the cognitive impairments observed in patients with WMHL.

The feasibility and satisfaction study of 5G-based robotic teleultrasound diagnostic system in health check-ups.

Objective: Regular check-up with ultrasound in underserved rural and/or remote areas is hampered due to the limited availability of sonologists and ultrasound devices. This study aimed to assess the feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system. Methods: In this prospective study, sonologists from two hospitals manipulated the telerobotic ultrasound system to perform teleultrasound check-ups of the liver, gallbladder, pancreas, spleen, kidneys, bladder, prostate (male), uterus and ovaries (female) for the subjects. The feasibility and satisfaction of health check-ups with a 5G-based robotic teleultrasound diagnostic system were evaluated in terms of examination results, examination duration, and satisfaction questionnaire survey. Results: A total of 546 subjects were included with the most frequently diagnosed being abdominal disorders (n = 343) and male reproductive illnesses (n = 97), of which fatty liver (n = 204) and prostatic calcification (n = 54) were the most. The median teleultrasound examination duration (interquartile range) for men and women was 9 (9-11) min and 9 (7-11) min (p = 0.236), respectively. All the subjects were satisfied with this new type of telerobotic ultrasound check-ups and 96% reported no fear of the robotic arm during the examination. Conclusion: The 5G-based teleultrasound robotic diagnostic system in health check-ups is feasible and satisfactory, indicating that this teleultrasound robot system may have significant application value in underserved rural and/or remote areas to mitigate disparity in achieving health equity.

Low-dose apatinib in subjects with renal impairment: A pharmacokinetics study.

OBJECTIVE: In patients with renal impairment, we studied apatinib and its major metabolites (M1-1, M1-2, M1-6, and M9-2) for pharmacokinetics. METHODS: Subjects with different renal functions were given a single oral dose of apatinib mesylate tablets of 250 mg. Pharmacokinetic samples were collected at 1 hour before dosing,0.25, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, and 96 h after dosing. The pharmacokinetic parameters of apatinib and its major metabolites were calculated by noncompartmental analysis. RESULTS: Comparing PK parameters of the mild or moderate renal impairment group with the healthy group: the geometric mean ratios of maximum observed drug concentration (Cmax), the area under the plasma drug concentration-time curve from time 0 to the final quantifiable time (AUC0-t), and the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) were all about one. No significant effect of mild and moderate renal impairment on apatinib pharmacokinetics was observed. Mild and moderate renal impairment was also not observed to have a significant effect on the pharmacokinetics of metabolites M1-1, M1-2, and M1-6. However, mild and moderate renal impairment had a certain increase in exposure to the metabolite M9-2. Considering that M9-2 has no inhibitory effect on protein tyrosine kinase, it has no clinical significance. In addition, the proportion of cumulative excretion of apatinib and its major metabolites was small and almost negligible in all three groups of subjects. CONCLUSION: Patients with mild and moderate renal impairment do not need to adjust the dose of apatinib when using low dose (250 mg) apatinib.

Prognostic impact of white blood cell counts on clinical outcomes in patients with chronic renal insufficiency undergoing percutaneous coronary intervention.

Objective: To determine whether the inclusion of white blood cell (WBC) counts in the SYNTAX score (SS) or SS II models could improve the models' performance for risk stratification in individuals with chronic renal insufficiency (CRI) following percutaneous coronary intervention (PCI). Methods: In total, 2,313 patients with CRI, who were subjected to PCI and had data available on in-hospital WBC (ih-WBC) counts, were recruited. Patients were divided into 3 groups as per their ih-WBC counts (low, medium, and high). The primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints incorporated myocardial infarction, stroke, unplanned revascularization, and major adverse cardiovascular and cerebrovascular events (MACCEs). Results: During a median follow-up of 3 years, the high WBC group had the highest incidences of CM (2.4% vs. 2.1% vs. 6.7%; p < 0.001), ACM (6.3% vs. 4.1% vs. 8.2%; p < 0.001), unplanned revascularization (8.4% vs. 12.4% vs. 14.1%; p < 0.001), and MACCEs (19.3% vs. 23.0% vs. 29.2%; p < 0.001) among the three groups. Multivariable Cox regression analysis depicted that the risk of ACM and CM in the high WBC group was 2.577 (95% confidence interval [CI]: 1.504-4.415, p < 0.001) and 3.850 (95% CI: 1.835-8.080, p < 0.001) times that in the low WBC group after adjusting for other confounding factors. A combination of ih-WBC counts with SS or SS II significantly improved the risk assessment and prediction of ACM and CM. Conclusion: The ih-WBC counts was associated with the risk of occurrence of ACM, CM, unplanned revascularization, and MACCEs in individuals with CRI following PCI. It provides an incremental predictive value for the occurrence of ACM and CM when included in SS or SS II models.

Ultrasound super-resolution imaging for the differential diagnosis of thyroid nodules: A pilot study.

Objective: Ultrasound imaging provides a fast and safe examination of thyroid nodules. Recently, the introduction of super-resolution imaging technique shows the capability of breaking the Ultrasound diffraction limit in imaging the micro-vessels. The aim of this study was to evaluate its feasibility and value for the differentiation of thyroid nodules. Methods: In this study, B-mode, contrast-enhanced ultrasound, and color Doppler flow imaging examinations were performed on thyroid nodules in 24 patients. Super-resolution imaging was performed to visualize the microvasculature with finer details. Microvascular flow rate (MFR) and micro-vessel density (MVD) within thyroid nodules were computed. The MFR and MVD were used to differentiate the benign and malignant thyroid nodules with pathological results as a gold standard. Results: Super-resolution imaging (SRI) technique can be successfully applied on human thyroid nodules to visualize the microvasculature with finer details and obtain the useful clinical information MVD and MFR to help differential diagnosis. The results suggested that the mean value of the MFR within benign thyroid nodule was 16.76 ± 6.82 mm/s whereas that within malignant thyroid was 9.86 ± 4.54 mm/s. The mean value of the MVD within benign thyroid was 0.78 while the value for malignant thyroid region was 0.59. MFR and MVD within the benign thyroid nodules were significantly higher than those within the malignant thyroid nodules respectively (p < 0.01). Conclusions: This study demonstrates the feasibility of ultrasound super-resolution imaging to show micro-vessels of human thyroid nodules via a clinical ultrasound platform. The important imaging markers, such as MVD and MFR, can be derived from SRI to provide more useful clinical information. It has the potential to be a new tool for aiding differential diagnosis of thyroid nodules.

Ultrasound super-resolution imaging for differential diagnosis of breast masses.

Objective: Ultrasound imaging has been widely used in breast cancer screening. Recently, ultrasound super-resolution imaging (SRI) has shown the capability to break the diffraction limit to display microvasculature. However, the application of SRI on differential diagnosis of breast masses remains unknown. Therefore, this study aims to evaluate the feasibility and clinical value of SRI for visualizing microvasculature and differential diagnosis of breast masses. Methods: B mode, color-Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS) images of 46 patients were collected respectively. SRI were generated by localizations of each possible contrast signals. Micro-vessel density (MVD) and microvascular flow rate (MFR) were calculated from SRI and time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were obtained by quantitative analysis of CEUS images respectively. Pathological results were considered as the gold standard. Independent chi-square test and multivariate logistic regression analysis were performed using these parameters to examine the correlation. Results: The results showed that SRI technique could be successfully applied on breast masses and display microvasculature at a significantly higher resolution than the conventional CDFI and CEUS images. The results showed that the PI, AUC, MVD and MFR of malignant breast masses were significantly higher than those of benign breast masses, while TTP was significantly lower than that of benign breast masses. Among all five parameters, MVD showed the highest positive correlation with the malignancy of breast masses. Conclusions: SRI is able to successfully display the microvasculature of breast masses. Compared with CDFI and CEUS, SRI can provide additional morphological and functional information for breast masses. MVD has a great potential in assisting the differential diagnosis of breast masses as an important imaging marker.

Oral Microbiota and Tumor-A New Perspective of Tumor Pathogenesis.

Microorganisms have long been known to play key roles in the initiation and development of tumors. The oral microbiota and tumorigenesis have been linked in epidemiological research relating to molecular pathology. Notably, some bacteria can impact distal tumors by their gastrointestinal or blood-borne transmission under pathological circumstances. Certain bacteria drive tumorigenesis and progression through direct or indirect immune system actions. This review systemically discusses the recent advances in the field of oral microecology and tumor, including the oncogenic role of oral microbial abnormalities and various potential carcinogenesis mechanisms (excessive inflammatory response, host immunosuppression, anti-apoptotic activity, and carcinogen secretion) to introduce future directions for effective tumor prevention.

Accumulation of microplastics and Tcep pollutants in agricultural soil: Exploring the links between metabolites and gut microbiota in earthworm homeostasis.

Agricultural soil contamination with plastic film has become a critical global environmental problem, requiring greater research on the possible occurrence and biological risk of microplastics (MPs) and their additives in soil ecosystems. The presence of MPs and tris (2-chloroethyl) phosphate (Tcep) in agricultural soil was investigated at nine sites in the present study. Polyethylene MPs (PE-MPs) and Tcep were found at all nine sites. To study co-exposure effects on soil microbiota and earthworms, and to mimic a realistic exposure scenario, 0.05 % (w/w) PE-MPs with three particle size ranges were combined with Tcep (1.0 mg/kg). After 28 days of exposure, there was no indication that added PE-MPs and/or Tcep significantly affected the soil microbial community structure. In earthworms, size-selective intake, digestion and egestion of PE-MPs may occur, with Tcep co-exposure affecting the residual Tcep concentration in earthworm intestines (3.52-9.31 µg/g dw). Long-term earthworm PE-MPs intake caused intestinal damage, and Tcep co-exposure increased oxidative stress, thereby influencing their feeding behavior and growth, resulting in weight loss (3.42 %-14.96 %), especially for the most common PE-MPs sizes (0-300 µm). High performance liquid chromatography-mass spectrometry (LC-MS) was used for metabolomic analysis, revealing the significant up-regulation of citrate (p < 0.001) and down-regulation of l-glutamate (p < 0.05) in co-exposure groups. Co-exposure resulted in the alteration of most metabolic pathways, thereby impairing nervous, digestive and excretory systems in the earthworm, with an associated decrease in amino acid metabolism and changes in tricarboxylic acid (TCA) cycle intermediates. Gut microbiota, such as Proteobacteria (Verminephrobacter and Bradyrhizobium) and Firmicutes (Bacillus), are critically important in maintaining earthworm metabolic homeostasis, particularly for the TCA cycle and amino acid metabolism. Overall, MPs and Tcep co-exposure in agricultural soil enhanced their toxicity to earthworms and may potentially endanger the development of agricultural sustainability.

The guiding value of hybrid resting full-cycle ratio and fractional flow reserve strategy for percutaneous coronary intervention in a Chinese real-world cohort with non-ST elevation acute coronary syndrome.

Objective: The study aimed to assess the correlation and agreement between resting full-cycle ratio (RFR) and fractional flow reserve (FFR), and evaluate the guiding value of a hybrid RFR-FFR strategy for percutaneous coronary intervention (PCI) in a Chinese real-world cohort with non-ST elevation acute coronary syndrome (NSTE-ACS). Materials and methods: A total of 109 patients with NSTE-ACS (149 diseased vessels), who underwent an invasive physiological assessment in Cangzhou Central Hospital, Hebei Medical University, were prospectively enrolled from September 2021 to May 2022. FFR ≤ 0.80 was used as the gold standard for coronary artery functional ischemia. We utilized the Pearson correlation and Bland-Altman analysis to assess the correlation and agreement between RFR and FFR. The diagnostic value of RFR predicting FFR ≤ 0.80 was evaluated in accordance with the receiver operating characteristic (ROC) curve. The hybrid RFR-FFR strategy, which was established according to determining the "gray zone" of RFR (FFR was further assessed using vasodilators only for diseased vessels in the "gray zone"), needed to afford over 95% global agreement with the FFR-only strategy. Results: Resting full-cycle ratio was significantly linearly linked with FFR (R 2 = 0.636, P < 0.001). The accuracy, specificity, and sensitivity for RFR ≤ 0.89 predicting FFR ≤ 0.80 were 81.2, 70.8, and 86.1%, respectively. The area under the ROC curve for RFR predicting FFR ≤ 0.80 was 0.881 (P < 0.001), and the cutoff value was 0.90. The "gray zone" of RFR was 0.85-0.93. The positive and negative predictive values of the hybrid RFR-FFR strategy were 0.95 and 0.93, respectively. The hybrid RFR-FFR strategy exhibited an agreement of 96.0% with FFR and obviated the need for a vasodilator by 60.4%. Conclusion: Resting full-cycle ratio and FFR have high correlation and consistency. The hybrid RFR-FFR strategy highlights considerably enhanced agreement with the FFR-only strategy, whilst making the requirement of vasodilator administration less than a half.

Abnormal functional connectivity in the right dorsal anterior insula associated with cognitive dysfunction in patients with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic disease with a high incidence worldwide. T2DM can cause cognitive impairment, but its neuropathological basis is unclear. A variety of neuropsychiatric studies have found that abnormal functional connectivity (FC) in the central executive network (CEN), default-mode network (DMN), and salience network (SN) may be the neuropathological basis of cognitive dysfunction. The right dorsal anterior insula (dAI) is the core SN area. It plays an important role in regulating the CEN and the DMN. However, few studies have explored the relationship between cognitive impairment and FC among the right dAI, CEN, and DMN in patients with T2DM. METHODS: Resting-state functional magnetic resonance imaging was used to investigate FC between the right dAI and the CEN and DMN in 44 patients with T2DM and 41 sex-, age-, and education-matched healthy controls, as well as its relationship with clinical/cognitive variables. RESULTS: In patients with T2DM, FC between the right dAI and multiple brain regions of the CEN and DMN was generally decreased, and FC strength between the right dAI and the inferior frontal gyrus negatively correlated with trail making test A score (r = -0.421, p = 0.004). CONCLUSIONS: Patients with T2DM exhibit abnormal FC between the right dAI and the CEN and DMN. This may be one of the neuromechanisms of cognitive impairment in patients with T2DM. In addition, reduced FC between the right dAI and the right inferior frontal gyrus may be related to abnormal attention regulation in patients with T2DM.

Altered Functional Topological Organization in Type-2 Diabetes Mellitus With and Without Microvascular Complications.

Microvascular complications can accelerate cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and have a high impact on their quality of life; however, the underlying mechanism is still unclear. The complex network in the human brain is the physiological basis for information processing and cognitive expression. Therefore, this study explored the relationship between the functional network topological properties and cognitive function in T2DM patients with and without microvascular complications (T2DM-C and T2DM-NC, respectively). Sixty-seven T2DM patients and 41 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological assessment. Then, graph theoretical network analysis was performed to explore the global and nodal topological alterations in the functional whole brain networks of T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. The T2DM-C group exhibited significantly higher local efficiency (Eloc), normalized cluster coefficient (γ), and small-world characteristics (σ) than the HCs. Patients with T2DM at different clinical stages (T2DM-C and T2DM-NC) showed varying degrees of abnormalities in node properties. In addition, compared with T2DM-NC patients, T2DM-C patients showed nodal properties disorders in the occipital visual network, cerebellum and middle temporal gyrus. The Eloc metrics were positively correlated with HbA1c level (P = 0.001, r = 0.515) and the NE values in the right paracentral lobule were negatively related with serum creatinine values (P = 0.001, r = -0.517) in T2DM-C patients. This study found that T2DM-C patients displayed more extensive changes at different network topology scales. The visual network and cerebellar may be the central vulnerable regions of T2DM-C patients.