Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

The value of microvascular Doppler ultrasound technique, qualitative or quantitative shear-wave elastography of breast lesions for predicting axillary nodal burden in patients with breast cancer.

Background: The status of the axillary lymph node (ALN) in patients with breast cancer can critically inform clinical decision-making and prognosis. Preoperative evaluation of limited nodal burden (0-2 metastatic ALNs) and high nodal burden (≥3 metastatic ALNs) is vital for individual treatment in patients with breast cancer. Thus, this study aimed to evaluate the value of Angio-PLUS (AP; Aixplorer, SuperSonic Imagine) and the qualitative and quantitative shear-wave elastography (SWE) of breast lesions to predict limited or high axillary nodal burden and to develop a model for predicting limited or high axillary nodal burden. Methods: From March 2020 to November 2022, a total of 232 consecutive patients with breast cancer comprising 232 breast lesions were enrolled retrospectively from Yueyang Central Hospital. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and area under the receiver operating characteristic curve (AUC) of AP, qualitative SWE, quantitative SWE, and the predictive model for evaluating limited or high axillary nodal burden were compared. Results: There was no significant difference in AP patterns between the limited nodal burden group and high nodal burden group. The best cutoff values of Emin (the minimal value of the first Q-box), Emean (the mean value of the first Q-box), Emax (the maximum value of the first Q-box), Eratio (ratio of the first Q-Box and the second Q-Box) and standard deviation for predicting limited or high nodal burden were 80.85 KPa, 133.45 KPa, 153.40 KPa, 9.95, and 19.25 KPa, respectively. The Emax had the highest AUC, and its sensitivity, specificity, PPV, NPV, accuracy, and AUC were 71.64%, 56.36%, 40.00%, 83.04%, 60.78%, and 0.640 [95% confidence interval (CI): 0.575-0.702], respectively. The sensitivity, specificity, PPV, NPV, accuracy, and AUC of seven color patterns for qualitative SWE were 71.64%, 74.55%, 53.33%, 86.62%, 73.71%, and 0.731 (95% CI: 0.669-0.787), respectively, which was significantly higher than all the other quantitative SWE parameters. ALN evaluation in ultrasound and qualitative SWE were independent risk factors for predicting limited or high nodal burden according to a binary logistics regression analysis. The AUC of the predictive model based on independent risk factors was 0.820 (95% CI: 0.765-0.867), which was significantly higher than that of the other independent risk factors. Conclusions: The seven color patterns in the qualitative SWE of breast lesions were valuable for predicting limited or high nodal burden for patients with breast cancer. Compared with quantitative SWE, qualitative SWE exhibited a better diagnostic performance. Breast lesions present no findings, vertical stripes, and spot patterns were important indicators for limited nodal burden. The predictive model developed in this study could be a simple, noninvasive, and convenient method for predicting limited or high nodal burden, which would be beneficial for clinical decision-making and individual treatment to improve prognosis.

Ultrasound radiomics based on axillary lymph nodes images for predicting lymph node metastasis in breast cancer.

Objectives: To determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging. Methods: A total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared. Result: Radiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively. Conclusion: The radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.

Clinical efficacy of microwave in the treatment of axillary osmidrosis and primary hyperhidrosis.

Axillary osmidrosis (AO) and primary hyperhidrosis (PH) are common diseases, but there are still difficulties in treatment. Microwave therapy may become a new method. In order to evaluate long-time efficacy of patients with AO or PH treated by microwave and to discuss possible mechanism of microwave therapy by combining results of clinical and pathological, the study was carried out. Ten AO or PH patients with moderate or severe level were selected as subjects, and each subject received microwave treatment of bilateral armpits. The follow-up period lasted 2 years, and the changes of perspiration and odor were evaluated in subjective and objective ways. Each subject took skin biopsy in the treatment area before and after treatment or each follow-up. Hematoxylin-eosin and immunohistochemical staining were performed. Both subjective and objective index reflected the significant improvement of AO and PH after treatment (p < 0.05). Dermatology life quality index score decreased by 10.4 ± 4.6 (p < 0.05). The number of apocrine glands decreased significantly after treatment, and most of them changed from secretory phase to quiescent phase. In conclusion, microwave therapy can destroy apocrine sweat glands, reduce number of functional glands, so as to improve symptoms of AO and PH and elevate quality of life, which is safe, effective, and stable.

Upregulation of miR-128 Mediates Heart Injury by Activating Wnt/ß-catenin Signaling Pathway in Heart Failure Mice.

Cardiac hypertrophy contributes to heart failure and is pathogenically modulated by a network of signaling cascades including Wnt/ß-catenin signaling pathway. miRNAs have been widely demonstrated to regulate gene expression in heart development. miR-128 was routinely found as a brain-enriched gene and has been functionally associated with regulation of cardiac function. However, its role and molecular mechanisms that regulate cardiac hypertrophy remain largely unclear. Adeno-associated virus serotype 9 (AAV9)-mediated constructs with miR-128 or anti-miR-128 were generated and delivered to overexpression or blockade of miR-128 in vivo followed by HF induction with isoproterenol (ISO) or transverse aortic constriction (TAC). Cardiac dysfunction and hypertrophy, coupled with involved gene and protein level, were then assessed. Our data found that miR-128, Wnt1, and ß-catenin expressions were upregulated in both patients and mice model with HF. Interference with miR-128 reduces Wnt1/ß-catenin expression in mouse failing hearts and ameliorates heart dysfunctional properties. We identified miR-128 directly targets to Axin1, an inhibitor of Wnt/ß-catenin signaling, and suppresses its inhibition on Wnt1/ß-catenin. Our study provides evidence indicating miR-128 as an inducer of HF and cardiac hypertrophy by enhancing Wnt1/ß-catenin in an Axin1-dependent nature. We thus suggest miR-128 has potential value in the treatment of heart failure.

Distinct Function of Estrogen Receptors in the Rodent Anterior Cingulate Cortex in Pain-related Aversion.

BACKGROUND: Brain-derived estrogen is implicated in pain-related aversion; however, which estrogen receptors mediate this effect remains unclear. This study hypothesized that the different estrogen receptors in the rostral anterior cingulate cortex play distinct roles in pain-related aversion. METHODS: Formalin-induced conditioned place avoidance and place escape/avoidance paradigms were used to evaluate pain-related aversion in rodents. Immunohistochemistry and Western blotting were used to detect estrogen receptor expression. Patch-clamp recordings were used to examine N-methyl-D-aspartate-mediated excitatory postsynaptic currents in rostral anterior cingulate cortex slices. RESULTS: The administration of the estrogen receptor-ß antagonist 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP) or the G protein-coupled estrogen receptor-1 antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15) but not the estrogen receptor-α antagonist 1,3-bis (4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride (MPP) into the rostral anterior cingulate cortex blocked pain-related aversion in rats (avoidance score, mean ± SD: 1,3-bis [4-hydroxyphenyl]-4-methyl-5-(4-[2-piperidinylethoxy] phenol)-1H-pyrazole dihydrochloride (MPP): 47.0 ± 18.9%, 4-(2-phenyl-5,7-bis [trifluoromethyl] pyrazolo [1,5-a] pyrimidin-3-yl) phenol (PHTPP): -7.4 ± 20.6%, and [3aS*,4R*,9bR*]-4-[6-bromo-1,3-benzodioxol-5-yl]-3a,4,5,9b-3H-cyclopenta [c] quinolone (G15): -4.6 ± 17.0% vs. vehicle: 46.5 ± 12.2%; n = 7 to 9; P < 0.0001). Consistently, estrogen receptor-ß knockdown but not estrogen receptor-α knockdown by short-hairpin RNA also inhibited pain-related aversion in mice (avoidance score, mean ± SD: estrogen receptor-α-short-hairpin RNA: 26.0 ± 7.1% and estrogen receptor-ß-short-hairpin RNA: 6.3 ± 13.4% vs. control short-hairpin RNA: 29.1 ± 9.1%; n = 7 to 10; P < 0.0001). Furthermore, the direct administration of the estrogen receptor-ß agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) or the G protein-coupled estrogen receptor-1 agonist (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1) into the rostral anterior cingulate cortex resulted in conditioned place avoidance (avoidance score, mean ± SD: 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN): 35.3 ± 9.5% and (±)-1-([3aR*,4S*,9bS*]-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta [c]quinolin-8-yl)-ethanone (G1): 43.5 ± 22.8% vs. vehicle: 0.3 ± 14.9%; n = 8; P < 0.0001) but did not affect mechanical or thermal sensitivity. The activation of the estrogen receptor-ß/protein kinase A or G protein-coupled estrogen receptor-1/protein kinase B pathway elicited the long-term potentiation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. CONCLUSIONS: These findings indicate that estrogen receptor-ß and G protein-coupled estrogen receptor-1 but not estrogen receptor-α in the rostral anterior cingulate cortex contribute to pain-related aversion by modulating N-methyl-D-aspartate receptor-mediated excitatory synaptic transmission.

[Molecular mechanisms of NMDA receptor-MAPK-CREB pathway underlying the involvement of the anterior cingulate cortex in pain-related aversion].

The pain experience includes a sensory-discriminative component and an emotional-affective component. The great progress in the genetic, molecular, cellular and systemic levels on the study of the sensory dimension of pain has been made. However, the study of the emotional components of pain is relatively backward. A line of clinic observations indicates that chronic pain and pain-related negative emotion affect the physical and mental health of patients. This review summarizes the main progress from our and other laboratories regarding the affective component of pain, elaborates the neuronal mechanisms of pain-related aversive emotion in the anterior cingulate cortex (ACC), especially the critical role of NMDA receptors and ERK-CREB pathway. A variety of regulatory molecules, such as synapse associated protein SIP30 and estrogen contribute to pain-related aversive emotion via facilitating presynaptic glutamate release and postsynaptic NMDA receptor-mediated synaptic transmission. The far-reaching effects of pain-related negative emotion on patients with chronic pain are emphasized.

Hepatic Resection after Initial Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone for the Treatment of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies.

BACKGROUND: There is no consensus regarding the selection of treatment options for hepatocellular carcinoma (HCC) after initial transarterial chemoembolization (TACE). This meta-analysis aimed to explore the survival benefit of hepatic resection after initial TACE for the treatment of HCC. MATERIALS AND METHODS: We searched three major databases to identify all relevant papers comparing the outcomes of hepatic resection after initial TACE versus TACE alone for the treatment of HCC. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated to evaluate the survival benefit of hepatic resection after initial TACE over TACE alone. RESULTS: Three of 2,037 initially identified papers were included. All of them were cohort studies from Asia. There was a significantly better overall survival (OS) in patients undergoing hepatic resection after initial TACE than in those undergoing TACE alone (HR=0.63, 95%CI=0.52-0.76, P<0.00001). The heterogeneity among studies was not statistically significant (P=0.96; I2=0%). CONCLUSIONS: Hepatic resection could improve the OS of HCC patients treated initial TACE. Further randomized controlled trials are now necessary to identify the target populations for the sequential use of hepatic resection after initial TACE and to compare the outcomes between patients undergoing hepatic resection after initial TACE session versus those undergoing TACE alone.

Ridge expansion alone or in combination with guided bone regeneration to facilitate implant placement in narrow alveolar ridges: a retrospective study.

OBJECTIVE: To evaluate the long-term outcomes of ridge expansion technique in dealing with horizontal bony insufficiency of alveolar ridges for implant placement. MATERIALS AND METHODS: During the period 2004-2009, 168 patients with width insufficiency of alveolar ridges were treated using the ridge expansion technique to obtain an improved bony base for implant placement. Depending on the severity of width insufficiency, the surgical procedures were classified into two groups: ridge expansion alone (Group 1) and ridge expansion in combination with guided bone regeneration (Group 2). After 4-6 months of unloaded healing, the implants were restored. The patients were followed up until 2013 with clinical and radiographic examinations. RESULTS: Among the 168 patients, 11 patients underwent a fracture of labial/buccal bony plate during surgery, which was corrected by changing the procedure into bone grafting, yielding a surgical failure rate of 6.5%. In the remaining 157 patients successfully treated by ridge expansion alone or in combination with GBR, 226 implants were simultaneously placed as planned. No implant failed over 2.8 years (6 months to 8 years) of follow-up, yielding a cumulative implant survival rate of 100% in each group. Six implants in Group 1 and 4 implants in Group 2, although osseointegrated and in function, did not fulfill success criteria: Cumulative implants' success rates were 93.2% in Group 1 and 95.6% in Group 2. The mean marginal bone losses during the first year in Group 1 and Group 2 were 0.69 and 0.43 mm, respectively, followed by an annual loss of ~ 0.06 and 0.07 mm, respectively, in the following years. No clinical parameter was abnormal. Twenty-two (10.4%) implants were exposed to peri-implant mucositis, whereas 19 (11.0%) implant-supported restorations were involved in prosthetic complications. CONCLUSIONS: The preliminary results of this retrospective study indicate that ridge expansion alone or in combination with GBR can be considered an effective and safe procedure for treatment of width insufficiency of alveolar ridges on the purpose of implant application.