Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy.

Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

Prognostic implication of residual inflammatory trajectories in acute type I aortic dissection: dual-center prospective cohort study.

BACKGROUND: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. METHODS: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. RESULTS: 246 patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified (cluster α 45[18.3%], ß105 [42.7%], and γ 96 [39.0%]). Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI, 1.126, 12.574; P=0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination (the area under the receiver-operating characteristic curve 0.765, 95% CI [0.660-0.869]), calibration, and clinical utility. CONCLUSION: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.

Clinicopathological features, psychological status, and prognosis of 33 patients with occult breast cancer.

BACKGROUND: Occult breast cancer (OBC) has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer. Due to the small number of cases and limited clinical ex-perience, treatments vary greatly around the world and no standardized treat-ment has yet been established. AIM: To investigate the clinicopathological features, psychological status and prog-nostic features of patients with OBC. METHODS: The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed. The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale. Patients' emotions, stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule, the Chinese Perceived Stress Scale, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Patient survival was calculated using the Kaplan-Meier method, and survival curves were plotted for analysis with the log-rank test. Univariate and multivariate survival analyses were performed using the Cox regression model. RESULTS: The 33 OBC patients included 32 females and 1 male. Of the 33 patients, 30 (91%) had axillary tumors, 3 (9%) had a neck mass as the primary symptom; 18 (54.5%) had estrogen receptor-positive tumors, 17 (51.5%) had progesterone receptor-positive tumors, and 18 (54.5%) had Her-2-positive tumors; 24 (72.7%) received surgical treatment, including 18 patients who underwent modified radical mastectomy, 1 patient who underwent breast-conserving surgery plus axillary lymph node dissection (ALND), and 5 patients who underwent ALND alone; 12 patients received preoperative neoadjuvant therapy. All 30 patients developed anxiety and depression, with low positive affect scores and high negative affect scores, accompanied by a high stress level and poor psychological resilience. There were no differences in the psychological status of patients according to age, body mass index, or menopausal status. The overall survival and disease-free survival (DFS) of all the patients were 83.3% and 55.7%, respectively. Univariate analysis demonstrated that the initial tumor site (P = 0.021) and node stage (P = 0.020) were factors that may affect patient prognosis. The 5-year DFS rate of OBC patients who received radiotherapy was greater (P < 0.001), while the use of different surgical methods (P = 0.687) had no statistically significant effect on patient outcomes. Multivariate analysis revealed that radiotherapy (P = 0.031) was an independent prognostic factor. Receiving radiotherapy had a significant effect on the CD-RISC score (P = 0.02). CONCLUSION: OBC is a rare breast disease whose diagnosis and treatment are currently controversial. There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy. In addition, radiotherapy can significantly improve patient outcomes. We should pay attention to the psychological state of patients while they receive antitumor therapy.

Radiomics models based on enhanced computed tomography to distinguish clear cell from non-clear cell renal cell carcinomas.

This study was to assess the effect of the predictive model for distinguishing clear cell RCC (ccRCC) from non-clear cell RCC (non-ccRCC) by establishing predictive radiomic models based on enhanced-computed tomography (CT) images of renal cell carcinoma (RCC). A total of 190 cases with RCC confirmed by pathology were retrospectively analyzed, with the patients being randomly divided into two groups, including the training set and testing set according to the ratio of 7:3. A total of 396 radiomic features were computationally obtained and analyzed with the Correlation between features, Univariate Logistics and Multivariate Logistics. Finally, 4 features were selected, and three machine models (Random Forest (RF), Support Vector Machine (SVM) and Logistic Regression (LR)) were established to discriminate RCC subtypes. The radiomics performance was compared with that of radiologist diagnosis. In the testing set, the RF model had an area under the curve (AUC) value of 0.909, a sensitivity of 0.956, and a specificity of 0.538. The SVM model had an AUC value of 0.841, a sensitivity of 1.0, and a specificity of 0.231, in the testing set. The LR model had an AUC value of 0.906, a sensitivity of 0.956, and a specificity of 0.692, in the testing set. The sensitivity and specificity of radiologist diagnosis to differentiate ccRCC from non-ccRCC were 0.850 and 0.581, respectively, with the AUC value of the radiologist diagnosis as 0.69. In conclusion, radiomics models based on CT imaging data show promise for augmenting radiological diagnosis in renal cancer, especially for differentiating ccRCC from non-ccRCC.

Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow-derived mesenchymal stem cells via the PKA-AMPK-SIRT1 axis.

Osteoporosis is a bone disease characterized by reduced bone density, thin cortical bone and large gaps in the bone's honeycomb structure, which increases the risk of bone fragility. Uncarboxylated osteocalcin (unOC), a vitamin K-dependent bone protein, is known to regulate carbohydrate and energy metabolism. A previous study demonstrated that unOC promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts, but inhibits their differentiation into adipocytes. However, the underlying mechanism remains unknown. The present study showed that unOC regulated the differentiation potential of BMSCs via protein kinase A (PKA)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling. SIRT1, a member of the sirtuin family with deacetylation functions, was upregulated by unOC in BMSCs. Transfection analyses with SIRT1 small interfering RNA indicated that the unOC-induced differentiation shift in BMSCs required SIRT1. Examination of SIRT1 downstream targets revealed that unOC regulated the acetylation levels of runt-related transcription factor (RUNX) 2 and peroxisome proliferator-activated receptor γ (PPARγ). Therefore, unOC inhibited adipogenic differentiation by PPARγ acetylation and promoted osteogenic differentiation by RUNX2 deacetylation. Moreover, phosphorylated PKA and AMPK protein levels increased after unOC treatment, which led to the upregulation of SIRT1. Western blot analysis with PKA and AMPK inhibitors indicated that the PKA-AMPK signaling pathway functioned upstream of SIRT1 and positively regulated SIRT1 expression. These findings led us to propose a model in which unOC regulated BMSC osteogenic differentiation through the PKA-AMPK-SIRT1 axis, giving evidence towards the therapeutic potential of unOC in osteoporosis treatment.

Comparison of Different Machine Models Based on Contrast-Enhanced Computed Tomography Radiomic Features to Differentiate High From Low Grade Clear Cell Renal Cell Carcinomas.

PURPOSE: This study was to investigate the role of different radiomics models with enhanced computed tomography (CT) scan in differentiating low from high grade renal clear cell carcinomas. MATERIALS AND METHODS: CT data of 190 cases with pathologically confirmed renal cell carcinomas were collected and divided into the training set and testing set according to different time periods, with 122 cases in the training set and 68 cases in the testing set. The region of interest (ROI) was delineated layer by layer. RESULTS: A total of 402 radiomics features were extracted for analysis. Six of the radiomic parameters were deemed very valuable by univariate analysis, rank sum test, LASSO cross validation and correlation analysis. From these six features, multivariate logistic regression model, support vector machine (SVM), and decision tree model were established for analysis. The performance of each model was evaluated by AUC value on the ROC curve and decision curve analysis (DCA). Among the three prediction models, the SVM model showed a high predictive efficiency. The AUC values of the training set and the testing set were 0.84 and 0.83, respectively, which were significantly higher than those of the decision tree model and the multivariate logistic regression model. The DCA revealed a better predictive performance in the SVM model that possessed the highest degree of coincidence. CONCLUSION: Radiomics analysis using the SVM radiomics model has highly efficiency in discriminating high- and low-grade clear cell renal cell carcinomas.

Effect of cardiopulmonary bypass reoxygenation on myocardial dysfunction following pediatric tetralogy of Fallot repair.

BACKGROUND: Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. METHODS: We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6-72 months who underwent complete repair of tetralogy of Fallot in 2012-2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. RESULTS: This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5-39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3-16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040-3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. CONCLUSIONS: Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. TRIAL REGISTRATION: Clinical Trials. gov number NCT03568357. June 26, 2018.

Radiomics and Radiogenomics in Evaluation of Colorectal Cancer Liver Metastasis.

Colorectal cancer is one common digestive malignancy, and the most common approach of blood metastasis of colorectal cancer is through the portal vein system to the liver. Early detection and treatment of liver metastasis is the key to improving the prognosis of the patients. Radiomics and radiogenomics use non-invasive methods to evaluate the biological properties of tumors by deeply mining the texture features of images and quantifying the heterogeneity of metastatic tumors. Radiomics and radiogenomics have been applied widely in the detection, treatment, and prognostic evaluation of colorectal cancer liver metastases. Based on the imaging features of the liver, this paper reviews the current application of radiomics and radiogenomics in the diagnosis, treatment, monitor of disease progression, and prognosis of patients with colorectal cancer liver metastases.

Triport periareolar thoracoscopic surgery versus right minithoracotomy for repairing atrial septal defect in adults.

OBJECTIVES: Our goal was to investigate the safety and feasibility of triport periareolar thoracoscopic surgery (TPTS) and its advantages in repairing adult atrial septal defect. METHODS: Between January 2017 and January 2020, a total of 121 consecutive adult patients underwent atrial septal defect closure in our institution. Of these, 30 patients had TPTS and 31 patients had a right minithoracotomy (RMT). Operational data and clinical outcomes were compared between the 2 groups. RESULTS: The total operation time, cardiopulmonary bypass time and aortic cross-clamp time in the TPTS group were slightly longer than those in the RMT group, but there were no differences between the 2 groups. Compared with the RMT group, the TPTS group showed a decrease in the volume of chest drainage in 24 h (98.6 ± 191.2 vs 222.6 ± 217.2 ml; P = 0.032) and a shorter postoperative hospital stay (6.5 ± 1.5 vs 8.0 ± 3.7 days; P = 0.042). The numeric rating scale on postoperative day 7 was significantly less in the TPTS group than in the RMT group (2.82 ± 1.14 vs 3.56 ± 1.42; P = 0.034). The patient satisfaction scale for the cosmetic results in the TPTS group was significantly higher than in the RMT group (4.68 ± 0.55 vs 4.22 ± 0.76; P = 0.012). No differences were found in postoperative complications. No in-hospital death or major adverse events occurred in the 2 groups. CONCLUSIONS: TPTS is safe and feasible for the closure of adult atrial septal defect. Compared with RMT, it has been associated with less pain and better cosmetic outcomes.

Molecular properties and gut health benefits of enzyme-hydrolyzed konjac glucomannans.

Konjac glucomannan (KGM) with a molecular weight (MW) of 823.4 kDa was partially degraded by endo-1,4-ß-mannanase. Two hydrolyzed KGM fractions (KGM-M-1: 147.2 kDa and KGM-M-2: 21.5 kDa) were characterized and applied to the animal tests in comparison with the native KGM. After oral feeding to the mice, KGM-M-1 and KGM-M-2 significantly increased the levels of short chain fatty acids (SCFAs) in the colonic contents and the native KGM increased the SCFAs in the cecum. The more significant effect of the native KGM in the cecum may be attributable to its high viscosity, slowing down the movement of intestinal microflora through the cecum, while the lower MW KGM-M-1 and KGM-M-2 could move more easily through the colon to be fermented by colonic bacteria. This new finding may be useful for future research and development of low-MW KGM polysaccharides through enzyme hydrolysis for the desired gut health benefits.

Physicochemical and rheological properties of pomelo albedo pectin and its interaction with konjac glucomannan.

Pomelo albedo was extracted with water to obtain the high methoxyl pectin, labeled as PAP. The physicochemical and rheological properties of PAP were determined. The effects of PAP addition on rheological property and thermal stability of konjac glucomannan (KGM) were evaluated. Results indicated that PAP was composed of arabinose, glucose and galacturonic acid with a relative mass percentage of 7.2%: 9.5%: 83.3%, and exhibited an average molecular weight of 56.6 kDa. The degree of esterification of PAP was 65.5%, showing PAP was a kind of high methoxyl pectin. Apparent viscosity of PAP was concentration-dependently increased, while it was slightly enhanced with salt (NaCl or CaCl2) addition. Moreover, the addition of PAP declined the apparent viscosity, elastic property and thermal stability of KGM. It can be concluded that interaction was occurred between KGM and PAP. Meanwhile, the interaction mechanism between KGM and PAP has been preliminarily proposed. The present study can provide some references for the application of PAP and support the combination usage of this pectin and KGM in food and other industries.

Uncarboxylated osteocalcin ameliorates hepatic glucose and lipid metabolism in KKAy mice via activating insulin signaling pathway.

Osteocalcin, expressed in osteoblasts of the bone marrow, undergoes post-translational carboxylation and deposits in mineralized bone matrix. A portion of osteocalcin remains uncarboxylated (uncarboxylated osteocalcin, GluOC) that is released into blood where it functions as a hormone to regulate insulin secretion and insulin sensitivity. As insulin resistance is closely associated with metabolic syndrome, this study is aimed to elucidate how GluOC regulates glucose and lipid metabolism in KKAy mice, an animal model displaying obese, hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. GluOC (3, 30 ng/g per day, ig) was orally administered to female KKAy mice for 4 weeks. Whole-body insulin sensitivity, glucose metabolism, hepatic steatosis, dyslipidemia were examined using routine laboratory assays. We found that GluOC administration significantly enhanced insulin sensitivity in KKAy mice by activating hepatic IRß/PI3K/Akt pathway and elevated the whole-body insulin sensitivity with decreased FPI and HOMA-IR index. Furthermore, GluOC administration alleviated hyperglycemia through suppressing gluconeogenesis and promoting glycogen synthesis in KKAy mice and in cultured hepatocytes in vitro. Moreover, GluOC administration dose-dependently ameliorated dyslipidemia and attenuated hepatic steatosis in KKAy mice by inhibiting hepatic de novo lipogenesis and promoting fatty-acid ß-oxidation. These results demonstrate that GluOC effectively enhances hepatic insulin sensitivity, improves hyperglycemia and ameliorates hepatic steatosis in KKAy mice, suggesting that GluOC could be a promising drug candidate for treating metabolic syndrome.

An innovative three-dimensional method for identifying a proper femoral intramedullary entry point in total knee arthroplasty.

BACKGROUND:: Identification of the proper femoral intramedullary (IM) access point is an important determinant of final implant position in IM-guided total knee arthroplasty (TKA). The aim of this study was to identify the optimal entry point in Chinese participants using a new three-dimensional method. METHODS:: A series of computed tomography scans of 44 femurs in Chinese participants from October 2014 to October 2015 were imported into Mimics 17.0 software to identify the optimal entry point. The apex of the intercondylar notch (AIN) was used as the reference bony anatomical landmark to identify the proper entry point to insert the IM rod. The statistical significance was calculated on the basis of a 5% level (P < 0.05) using the Student's t-test. RESULTS:: For the males, the average ideal entry point was 1.49 mm medial and 13.39 mm anterior to the AIN. The values were 1.77 mm medial and 15.29 mm anterior to the AIN in females. A significant difference was present between males and females (13.39 ± 2.46 mm vs. 15.29 ± 3.44 mm, t = 2.124, P = 0.040). When using the recommended location as the entry point for the IM rod, the mean potential error differed significantly from the femoral trochlear groove (the potential error of IM in males in coronal plane: 0.93° ± 0.24° vs. 1.27° ± 0.32°, t = -4.166, P <0.001; the potential error of IM in males in sagittal plane: 1.40° ± 0.42° vs. 2.79° ± 0.70°, t = 7.155, P < 0.001; the potential error of IM in females in coronal plane: 0.73° ± 0.28° vs. 1.15° ± 0.35°, t = 3.940, P < 0.001; and the potential error of IM in females in sagittal plane: 1.48° ± 0.47° vs. 2.76° ± 0.83°, t =5.574, P < 0.001). A significant difference was present between the recommended point and the point 10 mm anterior to the origin of the posterior cruciate ligament (the potential error of IM in males in coronal plane: 0.93° ± 0.24° vs. 1.53° ± 0.43°, t = 5.948, P < 0.001; the potential error of IM in males in sagittal plane: 1.40° ± 0.42° vs. 2.15° ± 0.75°, t = 3.152, P = 0.003; the potential error of IM in females in coronal plane: 0.73° ± 0.28° vs. 1.28° ± 0.42°, t = -4.632, P < 0.001; and the potential error of IM in females in sagittal plane: 1.48° ± 0.47° vs. 2.40° ± 0.93°, t = 3.763, P = 0.001). CONCLUSIONS: The technique described here is an innovative method for swift, easy, and accurate access to the medullary canal during TKA, and it can optimize the position and orientation of the prosthetic components in knee arthroplasty.

Glycosaminoglycan Content of the Lateral Compartment Cartilage in Knees Conforming to the Indications for Oxford Medial Unicompartmental Knee Arthroplasty.

BACKGROUND: The quality of the lateral compartment cartilage is important to preoperative evaluation and prognostic prediction of unicompartmental knee arthroplasty (UKA). Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables noninvasive assessment of glycosaminoglycan (GAG) content in cartilage. This study aimed to determine the GAG content of the lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA. METHODS: From December 2016 to May 2017, twenty patients (20 osteoarthritic knees) conforming to the indications for Oxford medial UKA were included as the osteoarthritis (OA) group, and 20 healthy volunteers (20 knees) paired by sex, knee side, age (±3 years), and body mass index (BMI) (±3 kg/m2) were included as the control group. The GAG contents of the weight-bearing femoral cartilage (wbFC), the posterior non-weight-bearing femoral cartilage (pFC), the lateral femoral cartilage (FC), and tibial cartilage (TC) were detected using dGEMRIC. The dGEMRIC indices (T1Gd) were calculated in the middle three consecutive slices of the lateral compartment. Paired t-tests were used to compare the T1Gd in each region of interest between the OA group and control group. RESULTS: The average age and BMI in the two groups were similar. In the OA group, T1Gd of FC and TC was 386.7 ± 50.7 ms and 429.6 ± 59.9 ms, respectively. In the control group, T1Gd of FC and TC was 397.5 ± 52.3 ms and 448.6 ± 62.5 ms, respectively. The respective T1Gd of wbFC and pFC was 380.0 ± 47.8 ms and 391.0 ± 66.3 ms in the OA group and 400.3 ± 51.5 ms and 393.6 ± 57.9 ms in the control group. Although the T1Gd of wbFC and TC tended to be lower in the OA group than the control group, there was no significant difference between groups in the T1Gd in any of the analyzed cartilage regions (P value of wbFC, pFC, FC, and TC was 0.236, 0.857, 0.465, and 0.324, respectively). CONCLUSIONS: The GAG content of the lateral compartment cartilage in knees conforming to indications for Oxford medial UKA is similar with those of age- and BMI-matched participants without OA.

Electrophysiological phenotypes of MeCP2 A140V mutant mouse model.

AIMS: MeCP2 gene mutations are associated with Rett syndrome and X-linked mental retardation (XLMR), diseases characterized by abnormal brain development and function. Recently, we created a novel MeCP2 A140V mutation mouse model that exhibited abnormalities of cell packing density and dendritic branching consistent with that seen in Rett syndrome patients as well as other MeCP2 mutant mouse models. Therefore, we hypothesized that some deficits of neuronal and synaptic functions might also be present in the A140V mutant model. METHODS: Here, we tested our hypothesis in hippocampal slices using electrophysiological recordings. RESULTS: We found that in young A140V mutant mice (3- to 4-week-old), hippocampal CA1 pyramidal neurons exhibited more positive resting membrane potential, increased action potential (AP) firing frequency induced by injection of depolarizing current, wider AP duration, and smaller after hyperpolarization potential compared to neurons prepared from age-matched wild-type mice, suggesting a neuronal hyperexcitation. At the synaptic level, A140V mutant neurons exhibited a reduced frequency of spontaneous IPSCs (inhibitory postsynaptic potentials) and an enhanced probability of evoked glutamate release, both suggesting neuronal hyperexcitation. However, hippocampal CA1 long-term potentiation was not significantly different between A140V and WT mice. In adult mice (11- to 13-month-old), in addition to neuronal hyperexcitation, we also found significant deficits of both short-term and long-term potentiation of CA3-CA1 synapses in A140V mice compared to WT mice. CONCLUSIONS: These results clearly illustrate the age-dependent abnormalities of neuronal and synaptic function in the MeCP2 A140V mutant mouse model, which provides new insights into the understanding of the pathogenesis of Rett syndrome.

Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices.

AIMS: To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity. METHODS: Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds). In addition, mitochondrial complex I function was measured using MitoSOX imaging in mitochondrial preparations. RESULTS: Acute exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3-CA1 synaptic transmission though 500 nM rotenone significantly reduced basal synaptic transmission. However, 50 nM rotenone significantly impaired LTP and this rotenone's effect was prevented by co-application of rotenone plus the ketones acetoacetate and ß-hydroxybutyrate (1 mM each). Finally, we measured mitochondrial function using MitoSOX imaging in mitochondrial preparations and found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM rotenone completely eliminated mitochondrial function. CONCLUSIONS: Our findings suggest that mitochondrial activity driven by complex I is a sensitive modulator of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to rotenone eliminates complex I function and in turn impairs LTP.