Geriatric nutritional risk index as a predictor for fragility fracture risk in elderly with type 2 diabetes mellitus: A 9-year ambispective longitudinal cohort study.

BACKGROUND & AIMS: The elderly are prone to fragility fractures, especially those suffering from type 2 diabetes mellitus (T2DM) combined with osteoporosis. Although studies have confirmed the association between GNRI and the prevalence of osteoporosis, the relationship between GNRI and fragility fracture risk and the individualized 10-year probability of osteoporotic fragility fractures estimated by FRAX remains unclear. This study aims to delve into the association between the GNRI and a fragility fracture and the 10-year probability of hip fracture (HF) and major osteoporotic fracture (MOF) evaluated by FRAX in elderly with T2DM. METHODS: A total of 580 patients with T2DM aged ≥60 were recruited in the study from 2014 to 2023. This research is an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 3.8 years through outpatient services, medical records, and home fixed-line telephone interviews. According to the tertiles of GNRI, all subjects were divided into three groups: low-level (59.72-94.56, n = 194), moderate-level (94.56-100.22, n = 193), and high-level (100.22-116.45, n = 193). The relationship between GNRI and a fragility fracture and the 10-year probability of HF and MOF calculated by FRAX was assessed by receiver operating characteristic (ROC) analysis, Spearman correlation analyses, restricted cubic spline (RCS) analyses, multivariable Cox regression analyses, stratified analyses, and Kaplan-Meier survival analysis. RESULTS: Of 580 participants, 102 experienced fragile fracture events (17.59%). ROC analysis demonstrated that the optimal GNRI cut-off value was 98.58 with a sensitivity of 75.49% and a specificity of 47.49%, respectively. Spearman partial correlation analyses revealed that GNRI was positively related to 25-hydroxy vitamin D [25-(OH) D] (r = 0.165, P < 0.001) and bone mineral density (BMD) [lumbar spine (LS), r = 0.088, P = 0.034; femoral neck (FN), r = 0.167, P < 0.001; total hip (TH), r = 0.171, P < 0.001]; negatively correlated with MOF (r = -0.105, P = 0.012) and HF (r = -0.154, P < 0.001). RCS analyses showed that GNRI was inversely S-shaped dose-dependent with a fragility fracture event (P < 0.001) and was Z-shaped with the 10-year MOF (P = 0.03) and HF (P = 0.01) risk assessed by FRAX, respectively. Multivariate Cox regression analysis demonstrated that compared with high-level GNRI, moderate-level [hazard ratio (HR) = 1.950; 95% confidence interval (CI) = 1.076-3.535; P = 0.028] and low-level (HR = 2.538; 95% CI = 1.378-4.672; P = 0.003) had an increased risk of fragility fracture. Stratified analysis exhibited that GNRI was negatively correlated with the risk of fragility fracture, which the stratification factors presented in the forest plot were not confounding factors and did not affect the prediction effect of GNRI on the fragility fracture events in this overall cohort population (P for interaction > 0.05), despite elderly females aged ≥70, with body mass index (BMI) ≥24, hypertension, and with or without anemia (all P < 0.05). Kaplan-Meier survival analysis identified that the lower-level GNRI group had a higher cumulative incidence of fragility fractures (log-rank, all P < 0.001). CONCLUSION: This study confirms for the first time that GNRI is negatively related to a fragility fracture and the 10-year probability of osteoporotic fragility fractures assessed by FRAX in an inverse S-shaped and Z-shaped dose-dependent pattern in elderly with T2DM, respectively. GNRI may serve as a valuable predictor for fragility fracture risk in elderly with T2DM. Therefore, in routine clinical practice, paying attention to the nutritional status of the elderly with T2DM and giving appropriate dietary guidance may help prevent a fragility fracture event.

The triglyceride glucose index as a sensitive predictor for the risk of MACCEs in patients with diabetic foot ulcers: An ambispective longitudinal cohort study.

The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.

Association Between Metabolic Dysfunction-Associated Fatty Liver Disease and MACCEs in Patients with Diabetic Foot Ulcers: An Ambispective Longitudinal Cohort Study.

Aim: Metabolic dysfunction-related fatty liver disease (MAFLD) is closely related to metabolic disorders. However, the relationship between MAFLD and the prognosis in diabetic foot ulcers (DFUs) remains unclear. This study aimed to explore the association between MAFLD and the risk of major adverse cardiac and cerebral events (MACCEs) in patients with DFUs. Methods: 889 inpatients with DFUs (PEDIS/TEXAS mild and above) were included in this study from 2013 to 2023. All participants were placed into non-MAFLD (n = 643) and MAFLD (n = 246) groups and followed up every 6 months for 10.9 years with a median of 63 months through in-person outpatient interviews and family fixed-line telephone visits. The association between MAFLD and the risk of MACCEs was evaluated through Multivariate Cox regression analyses, Stratified analyses and Kaplan-Meier survival analyses. Results: Of the 889 subjects, 214 (24.07%) experienced MACCEs. Multivariate Cox regression analysis showed that MAFLD was independently associated with MACCEs (P < 0.001), of which with non-fatal myocardial infarction (P = 0.04), non-fatal stroke (P = 0.047), coronary artery revascularization (P = 0.002), heart failure (P = 0.029), and all-cause mortality (P = 0.021), respectively. The stratified analysis revealed that compared with non-MAFLD (HR=1), DFUs with MAFLD had a 2.64-fold increased risk for MACCEs (P <0.001; P for interaction = 0.001) in peripheral arterial disease (PAD) subgroup. Kaplan-Meier analysis evidenced that the MAFLD group had a higher cumulative incidence of MACCEs (log-rank, all P < 0.05). Conclusion: MAFLD is a high-risk factor for MACCEs in patients with DFUs. The findings will remind clinicians to pay more attention to MAFLD in patients with DFUs, especially in patients with DFUs combined with PAD as early as possible in clinical practice and adopt timely effective intervention strategies to prevent the occurrence of MACCEs to improve the clinical prognosis in patients with DFUs.

The Ratio of Red Blood Cell Distribution Width to Albumin as a Predictor for Rehospitalization Risk and Rehospitalization All-Cause Mortality in Middle-Aged and Elderly Survivors with Sepsis: An Ambispective ICU Cohort Study.

Objective: To explore the relationship between red blood cell distribution width to albumin (RDW/ALB) ratio (RAR) and the risk of rehospitalization and rehospitalization all-cause mortality in middle-aged and elderly survivors with sepsis based on an ambispective longitudinal cohort from the Intensive Care Unit (ICU). Methods: Between 2017 and 2022, 455 adults who survived the first-episode severe sepsis without recurrence for at least 3 months were included in this study. All participants were followed up every 4 weeks for 12 months. According to the tertiles of RAR, participants were divided into three groups: low-level (≤0.36, n = 152), moderate-level (0.37-0.44, n = 152), and high-level (≥0.45, n = 151). The relationship between RAR and the risk of rehospitalization and rehospitalization all-cause mortality was evaluated. Results: Out of 455 participants, 156 experienced rehospitalization (34.3%), of which 44 (28.2%) died. Receiver operating characteristic (ROC) analysis showed that the RAR cut-off values for rehospitalization and rehospitalization all-cause mortality were 0.4251 and 0.4743, respectively. Multivariate Cox regression analysis indicated that the RAR was positively associated with rehospitalization (P = 0.011) and all-cause mortality (P = 0.006). Compared with the low-level, the high-level RAR presented a higher dose-dependent rehospitalization risk (P = 0.02) and rehospitalization all-cause mortality (P = 0.044). The stratified analysis displayed that compared to the low-level, with the RAR increasing by 1.0, the risk for rehospitalization increased 3.602-fold in aged <65 patients (P = 0.002) and 1.721-fold in female patients (P = 0.014). Kaplan-Meier survival analysis implied a significant positive association between the RAR and the cumulative incidence of rehospitalization and rehospitalization all-cause mortality (log-rank, all P < 0.001). Conclusion: RAR has a reliable predictive value for the risk of rehospitalization and rehospitalization all-cause mortality in patients with sepsis. Consequently, monitoring RAR for at least 1 year after surviving sepsis in female patients aged <65 in clinical practice is critical.

Triglyceride-glucose index is strongly associated with all-cause mortality in elderly females with diabetic foot ulcers: A 9-year follow-up study.

This study aims to explore the association between the triglyceride-glucose (TyG) index and all-cause mortality in patients with diabetic foot ulcers (DFUs) through an ambispective cohort study. A total of 555 inpatients with DFUs were qualified to participate in the trial study from 2013 to 2022. Throughout a median 63-month period, all subjects were followed up every 6 months. According to the three quantiles of the TyG index, participants were divided into three groups: low-level (≤8.75, n = 185), moderate-level (8.76-9.33, n = 185) and high-level (≥9.34, n = 185). The association between the TyG index and all-cause mortality in patients with DFUs was then assessed. During the follow-up period, out of 555 patients with DFUs, 116 died (20.9%). After adjusting for confounding factors, the TyG index was positively associated with all-cause mortality in patients with DFUs (HR = 1.733; 95% CI = 1.341-2.241; p < 0.001). Compared with the low-level TyG index, the moderate-level TyG index (HR = 1.685; 95% CI = 1.011-2.810; p = 0.045) and the high-level TyG index (HR = 2.769; 95% CI = 1.678-4.568; p < 0.001) were positively correlated with all-cause mortality in patients with DFUs. Additionally, in subgroup analysis, both females (HR = 1.905; 95% CI = 1.250-2.904; p = 0.003), males (HR = 1.729; 95% CI = 1.240-2.409; p = 0.001), younger (<65 years old) (HR = 1.467; 95% CI = 1.008-2.135; p = 0.046) and elderly (≥ 65) (HR = 1.933; 95% CI = 1.339-2.791; p < 0.001) showed a positive correlation between TyG index and all-cause mortality rate in patients with DFUs. Furthermore, in the high-level TyG index group compared, males (HR = 2.699; 95% CI = 1.457-4.998) and participants aged <65 years (HR = 2.031; 95% CI = 0.972-4.242), with the TyG index level increase by 1.0, the risk for all-cause mortality increased 3.277-fold in females (HR = 4.277; 95% CI = 1.645-11.124) and 1.909-fold in elderly aged ≥65 years (HR = 2.909; 95% CI = 1.486-5.695), respectively. Kaplan-Meier survival curve analysis showed that the higher the TyG index level, the higher risk of all-cause mortality in patients with DFUs (log-rank, all p < 0.001). Briefly, this study implies a strong positive correlation between the TyG index and all-cause mortality in patients with DFUs, especially in older women. Therefore, special attention should be paid to elderly females with DFUs because they have a higher TyG index level and risk of all-cause mortality than other populations in daily clinical practice.

Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Triglyceride Glucose Index is Strongly Associated with a Fragility Fracture in Postmenopausal Elderly Females with Type 2 Diabetes Mellitus Combined with Osteoporosis: A 6-Year Follow-Up Study.

Purpose: The triglyceride glucose (TyG) index serves as an indicator of insulin resistance (IR), which is also associated with bone metabolism. However, research on the relationship between the TyG index and a fragility fracture in individuals with type 2 diabetes mellitus (T2DM) or osteoporosis (OP) remains sparse. This study aims to explore the association between the TyG index and fragility fracture risk in postmenopausal elderly females with T2DM combined with OP based on an ambispective cohort study. Patients and Methods: A total of 220 postmenopausal women hospitalized with T2DM combined with OP between January 2015 and December 2020 were eligible for inclusion in this study. All participants were followed up every 6 months for 6 years with a median of 42 months. According to the tertiles of the TyG index, participants were divided into three groups: low-level (≤ 8.79, n =73), moderate-level (8.80-9.32, n=73), and high-level (≥ 9.33, n=74). The association between the TyG index and fragility fracture risk was then assessed. Results: Out of 220 patients, 46 experienced fragility fracture events (20.9%). Multivariate Cox regression analysis showed that the TyG index was positively associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Furthermore, compared to the low-level group, with the TyG index level increase by 1.0, the risk for fragility fracture increased 1.293-fold in the high-level group (HR=2.293, 95% CI=1.007-5.221, P < 0.05). Kaplan-Meier survival analysis indicated that fragility fractures were more likely to occur in patients with high levels of TyG index (log-rank, all P < 0.05). Conclusion: Our study showed that the TyG index was strongly associated with a fragility fracture in postmenopausal women with T2DM combined with OP. Therefore, special attention should be paid to postmenopausal elderly females with T2DM combined with OP in routine clinical practice.

A Novel Wound Therapy Modality: Autologous Wound Edge Dotted Full-Thickness Skin Grafting Improving Diabetic Foot Ulcer Healing.

Aim: To explore the therapeutic efficacy of autologous wound edge-dotted full-thickness skin grafting in improving diabetic foot ulcer healing. Methods: Sixty-three patients were divided into three groups: conventional wound therapy (CWT) (n = 23), platelet-rich plasma (PRP) (n = 20), and graft (n = 20). All participants were followed up for 12 weeks. The therapeutic efficacy of the three different wound treatment modalities was analyzed. Results: After follow-up, 37 (58.7%) patients showed complete wound re-epithelialization, of which 10 (43.5%) occurred in the CWT group, 14 (70.0%) in the PRP group, and 13 (65.0%) in the graft group. Multivariate Cox analysis showed that the independent predictive factors for ulcer healing were different treatment modalities (graft: HR = 3.214, 95% CI=1.300-7.945, P < 0.05; platelet-rich plasma: HR = 3.075, 95% CI=1.320-7.161, P < 0.01), ABI (HR = 9.917, 95% CI=2.675-36.760, P < 0.01), and TcPO2 (HR = 1.040; 95% CI=1.005-1.076; P < 0.05). Stratified analysis showed that higher ABI in graft group or PRP group had higher wound healing rate (graft group: HR = 3.748, 95% CI=1.210-11.607, P < 0.05; PRP group: HR = 5.029, 95% CI=1.743-14.509, P < 0.05); higher TcPO2 in the graft group had higher wound healing rate (HR = 15.805, 95% CI=4.414-56.594, P < 0.01). Additionally, the wound healing time (P < 0.0167) and cumulative healing rate (P < 0.05) in both the PRP group and graft group were more advantageous. The graft group promotes wound re-epithelialization earlier and faster than in the CWT group and PRP group (P < 0.05). Meanwhile, the graft group had lower medical costs (P < 0.0167). Conclusion: Autologous wound edge dotted full-thickness skin grafting has a higher cost-performance ratio than traditional diabetic foot ulcer wound care and is worthy of further clinical application.

The Ratio of Serum Uric Acid to Glycosylated Haemoglobin as a Predictor of All-Mortality in Elderly Patients with Diabetic Foot Ulcers: A Longitudinal Cohort Study.

Aim: To clarify the relationship between serum uric acid (UA) and glycosylated hemoglobin (UA/HbA1c) ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). Methods: A total of 172 inpatients with DFUs (PEDIS grades 2-4) were eligible for inclusion in this study from 2018 to 2023. This was a retrospective, longitudinal cohort study. All subjects were followed up every 6 months for a median of 60 months. According to the cutoff value of the UA/HbA1c ratio of 39.07 obtained from ROC analysis, the participants were divided into two groups: low-level (≤ 39.07, n = 107) and high-level (> 39.07, n = 65) groups. The correlation between UA/HbA1c ratio and all-cause mortality was also evaluated by Cox regression analysis TheKaplan-Meier survival curve analysis and Log rank tests were used to assess the incidence rates of all-cause mortality. The contribution rate of risk factors was estimated by the population-attributable risk percentage (PAR%) analysis. Results: ROC analysis showed that the optimal cutoff values for UA and the UA/HbA1c ratio were 372 µmol/L and 39.07, respectively. Multivariate Cox regression analysis indicated that a high UA/HbA1c ratio (HR =4.63; 95% CI = 2.004-10.7, P < 0.001) was independently associated with a high risk of all-cause mortality in patients with DFUs. Stratified analysis indicated that subjects aged ≥ 60 years had a greater risk of all-cause mortality associated with a high UA/HbA1c ratio (HR = 4.450; 95% CI = 1.711-11.574, P = 0.002). Kaplan-Meier survival analysis showed that all-cause mortality had a significant positive association with a high UA/HbA1c ratio (log-rank, P < 0.001) and a significant negative correlation with the lowered HbA1c level (< 6.5%) after a follow-up of 32 months (log-rank, P < 0.001). The population attributable risk percentage (PAR%) analysis suggested that the contribution rate of the high-level UA/HbA1c ratio to all-cause mortality was 33.7%, which was much greater than the 19.69% of UA. Conclusion: In brief, our study showed that for every 1.0% increase in the UA/HbA1c ratio, the all-cause mortality rate in elderly patients with DFUs aged ≥ 60 years increased by 3.45-fold. For elderly patients with DFUs, a safe and effective strategy to reduce all-cause mortality is to strictly control serum UA levels to < 372 µmol/L and appropriately loosen the control goal of HbA1c to ≥ 6.5%.

Examining the effects of second-and third-trimester gestational weight gain rates on the perinatal outcomes among Chinese twin pregnancies: a retrospective cohort study.

BACKGROUND: This paper investigated how second- and third-trimester gestational weight gain relates to perinatal outcomes among normal weight women with twin pregnancies in Fujian, China. METHODS: A retrospective study examining the medical records of 931 normal weight twin-pregnant women was conducted in Fujian Maternity and Child Health Hospital from 2014 to 2018.The 2nd and 3rdtrimester weekly weight gain rates were calculated, and women were categorized as gaining below, within, or above the 2009 Institute of Medicine (IOM) recommended rates. The association between the trimester-specific weight gain rate and perinatal outcome was determined by traditional regression analysis among groups. RESULTS: A total of 25.9%, 19.8% and 54.3% of women had rates of weight gain across the 2nd and 3rd trimesters less than, greater than or within the recommended rates respectively. Multivariate logistic regression analysis showed that weight gain greater than the recommended rate in the 2nd trimester was associated with a decreased risk of preeclampsia (aOR:0.489,95%CI:0.289 ~ 0.974). Weight gain less than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery(aOR:2.079, 95%CI:1.467 ~ 2.968), gestational diabetes mellitus (aOR: 2.048, 95%CI:1.411 ~ 2.971), intrahepatic cholestasis syndrome (aOR:3.015,95%CI: 1.058 ~ 8.587), pre-labour rupture of membrane (aOR: 1.708,95%CI: 1.169 ~ 2.493), average twin birth weight < 2500 g(aOR:1.532,95%CI: 1.125 ~ 2.084) and neonatal respiratory distress syndrome (aOR:4.934,95%CI:1.626 ~ 15.083) and was associated with decreased risks of caesarean section (aOR:0.589,95%CI:0.386 ~ 0.898) and preeclampsia (aOR:0.471, 95%CI:0.274 ~ 0.808). In addition, weight gain greater than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery (aOR:1.589,95%CI:1.428 ~ 2.951) and gestational hypertension (aOR:2.137,95% CI:1.034 ~ 4.415) as well as preeclampsia (aOR:2.246, 95%CI:1.462 ~ 3.452). The stratified analysis of weight gain in the 3rd trimester showed that there was no significant difference in the incidence of adverse pregnancy outcomes compared to the 2nd trimester weight gain groups. CONCLUSIONS: While this study showed that a gestational weight gain rate above or below the recommendation in the 3rd trimester was associated with some adverse maternal and neonatal outcomes, further prospective and multicentre studies are required to explore alternate ranges of gestational weight gain rates in twin pregnancies.

Targeted Delivery of Liposomal Temozolomide Enhanced Anti-Glioblastoma Efficacy through Ultrasound-Mediated Blood-Brain Barrier Opening.

Glioblastoma (GBM) is the commonest form of primary brain tumor in the central nervous system, with median survival below 15 months and only a 25% two-year survival rate for patients. One of the major clinical challenges in treating GBM is the presence of the blood-brain barrier (BBB), which greatly limits the availability of therapeutic drugs to the tumor. Ultrasound-mediated BBB opening provides a promising approach to help deliver drugs to brain tumors. The use of temozolomide (TMZ) in the clinical treatment of GBM has been shown to be able to increase survival in patients with GBM, but this improvement is still trivial. In this study, we developed a liposomal temozolomide formulation (TMZ-lipo) and locally delivered these nanoparticles into GBM through ultrasound-mediated BBB opening technology, significantly suppressing tumor growth and prolonging tumor-bearing animal survival. No significant side effects were observed in comparison with control rats. Our study provides a novel strategy to improve the efficacy of TMZ against GBM.

ER-α36 mediates gastric cancer cell invasion.

Estrogen evidently exerts a protective role against gastric cancer. Accordingly, we evaluated the relationship between the expression of the estrogen receptor ER-α36 and the clinicopathologic features in gastric cancer. ER-α36 expression levels differed among the tumor center, invasion front, and vascular metastases. The effects of E2ß (17ß-Estradiol, E2ß) on invasion ability in SGC7901, High36 (with ER-α36 upregulation), and Low36 (with ER-α36 downregulation) cells were evaluated using Transwell assays. Furthermore, the c-Src signaling pathway was inhibited using PP2 and the effects on E2ß-induced increases in E-cadherin, MMP2, and MMP9 were evaluated using western blotting. ER-α36, c-Src, MMP2, and E-cadherin levels were also evaluated in tumor xenografts. We found that 0.1 nM E2ß promoted gastric cancer cell invasion by reducing E-cadherin expression and increasing MMP2 and MMP9 levels. The upregulation of ER-α36 promoted gastric cancer cell invasion and the downregulation of ER-α36 reduced the invasive ability of cells. The levels of ER-α36, c-Src, and MMP2 were the highest in tumor xenografts using High36 cells, intermediate in tumor xenografts using SGC7901 cells, and lowest in tumor xenografts using Low36 cells. The opposite results were obtained for E-cadherin expression. ER-α36 enhanced gastric cancer cell invasion by the activation of membrane-initiated c-Src signaling pathways. In particular, treatment with E2ß and ER-α36 influenced gastric cancer cell invasion. Furthermore, c-Src was involved in the ER-α36-mediated estrogen signaling pathway and cell invasion.

[Changes of monocyte and monocyte-platelet aggregates in different subgroups of thrombotic events in patients with acute myocardial infarction during PCI].

Objective To investigate the impact of thrombotic events on the alterations of monocyte and monocyte-platelet aggregates (MPAs) in patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI). Methods Blood was collected before PCI for flow cytometry. Monocyte subsets and MPAs were detected by four-color platform (CDl4-APC, CDl6-PE-Cy7, CD86-PE and CD41-Alexa FluorR488). According to the expression of the platelet surface marker CD41, the number of monocyte subsets and MPAs was analyzed using the fluorescent microspheres of absolute counting tube. The Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis were performed. Results CD14+CD16++ monocytes in intraprocedural thrombotic events (IPTE) group were significantly fewer than those in non-IPTE group, and the percentage in total mononuclear cells decreased. Compared with non-IPTE group, MPA binding ratio and monocyte subset MPA binding ratio were significantly higher in IPTE group. ROC analysis showed that MPA binding ratio and subgroup MPA binding ratio had a better predictive value for IPTE in patients with AMI. Conclusion The CD14+CD16++ monocytes in IPTE group were significantly fewer than those in the non-IPTE group. MPA binding ratio and MPA binding ratio of monocyte subsets were significantly higher in the IPTE group than in the non-IPTE group, so they have a good predictive value for IPTE in patients with AMI.

Preparation and characterization of a novel silicon-modified nanobubble.

Nanobubbles (NBs) opened a new field of ultrasound imaging. There is still no practical method to control the diameter of bubbles. In this study, we developed a new method to control the size by incorporating of silicon hybrid lipids into the bubble membrane. The range of particle size of resulting NBs is between 523.02 ± 46.45 to 857.18 ± 82.90, smaller than the conventional microbubbles. The size of resulting NBs increased with the decrease in amount of silicon hybrid lipids, indicating the diameter of NBs can be regulated through modulating the ratio of silicon hybrid lipids in the bubble shell. Typical harmonic signals could be detected. The in vitro and in vivo ultrasound imaging experiments demonstrated these silicon-modified NBs had significantly improved ultrasound contrast enhancement abilities. Cytotoxicity assays revealed that these NBs had no obvious cytotoxicity to the 293 cell line at the tested bubble concentration. Our results showed that the novel NBs could use as nanoscale ultrasound contrast agents, providing the foundation for NBs in future applications including contrast-enhanced imaging and drug/gene delivery.

The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice.

Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer's disease (AD) rats through inhibition of Aß production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aß and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases.

Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice.

AIMS: This study investigated the neuroprotective properties of icariin (an effective component of traditional Chinese herbal medicine Epimedium) on neuronal function and brain energy metabolism maintenance in a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD). METHODS: 3 × Tg-AD mice as well as primary neurons were subjected to icariin treatment. Morris water maze assay, magnetic resonance spectroscopy (MRS), Western blotting, ELISA, and immunohistochemistry analysis were used to evaluate the effects of icariin administration. RESULTS: Icariin significantly improved spatial learning and memory retention in 3 × Tg-AD mice, promoted neuronal cell activity as identified by the enhancement of brain metabolite N-acetylaspartate level and ATP production in AD mice, preserved the expressions of mitochondrial key enzymes COX IV, PDHE1α, and synaptic protein PSD95, reduced Aß plaque deposition in the cortex and hippocampus of AD mice, and inhibited ß-site APP cleavage enzyme 1 (BACE1) expression. Icariin treatment also decreased the levels of extracellular and intracellular Aß1-42 in 3 × Tg-AD primary neurons, modulated the distribution of Aß along the neurites, and protected against mitochondrial fragmentation in 3 × Tg-AD neurons. CONCLUSIONS: Icariin shows neuroprotective effects in 3 × Tg-AD mice and may be a promising multitarget drug in the prevention/protection against AD.