Finite Element Analysis of Pelvic Floor Biomechanical Models to Elucidate the Mechanism for Improving Urination and Defecation Dysfunction in Older Adults: Protocol for a Model Development and Validation Study.

BACKGROUND: The population is constantly aging, and most older adults will experience many potential physiological changes as they age, leading to functional decline. Urinary and bowel dysfunction is the most common obstacle in older people. At present, the analysis of pelvic floor histological changes related to aging has not been fully elucidated, and the mechanism of improving intestinal control ability in older people is still unclear. OBJECTIVE: The purpose of this study is to describe how the finite element method will be used to understand the mechanical characteristics of and physiological changes in the pelvic cavity during the rehabilitation process, providing theoretical support for the mechanism for improving urination and defecation dysfunction in older individuals. METHODS: We will collect magnetic resonance imaging (MRI) and computed tomography (CT) data of the pelvic cavity of one male and one female volunteer older than 60 years and use the finite element method to construct a 3D computer simulation model of the pelvic cavity. By simulating different physiological states, such as the Valsalva maneuver and bowel movement, we will verify the accuracy of the constructed model, investigate the effects of different neuromuscular functional changes, and quantify the impact proportions of the pelvic floor muscle group, core muscle group, and sacral nerve. RESULTS: At present, we have registered the study in the Chinese Clinical Trial Registry and collected MRI and CT data for an older male and an older female patient. Next, the construction and analysis of the finite element model will be accomplished according to the study plan. We expect to complete the construction and analysis of the finite element model by July 2024 and publish the research results by October 2025. CONCLUSIONS: Our study will build finite element models of the pelvic floor of older men and older women, and we shall elucidate the relationship between the muscles of the pelvic floor, back, abdomen, and hips and the ability of older adults to control bowel movements. The results of this study will provide theoretical support for elucidating the mechanism for improving urination and defecation dysfunction through rehabilitation. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400080749; https://www.chictr.org.cn/showproj.html?proj=193428. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56333.

Comprehensive analysis of disulfidptosis-related genes: a prognosis model construction and tumor microenvironment characterization in clear cell renal cell carcinoma.

BACKGROUND: Disulfidptosis, a form of cell death induced by abnormal intracellular accumulation of disulfides, is a newly recognized variety of cell death. Clear cell renal cell carcinoma (ccRCC) is a usual urological tumor that poses serious health risks. There are few studies of disulfidptosis-related genes (DRGs) in ccRCC so far. METHODS: The expression, transcriptional variants, and prognostic role of DRGs were assessed. Based on DRGs, consensus unsupervised clustering analysis was performed to stratify ccRCC patients into various subtypes and constructed a DRG risk scoring model. Patients were stratified into high or low-risk groups by this model. We focused on assessing the discrepancy in prognosis, TME, chemotherapeutic susceptibility, and landscape of immune between the two risk groups. Finally, we validated the expression and explored the biological function of the risk scoring gene FLRT3 through in vitro experiments. RESULTS: The different subtypes had significantly different gene expression, immune, and prognostic landscapes. In the two risk groups, the high-risk group had higher TME scores, more significant immune cell infiltration, and a higher probability of benefiting from immunotherapy, but had a worse prognosis. There were also remarkable differences in chemotherapeutic susceptibility between the two risk groups. In ccRCC cells, the expression of FLRT3 was shown to be lower and its overexpression caused a decrease in cell proliferation and metastatic capacity. CONCLUSIONS: Starting from disulfidptosis, we established a new risk scoring model which can provide new ideas for doctors to forecast patient survival and determine clinical treatment plans.

Diagnostic efficacy of a combination of the Chinese thyroid imaging reporting and data system and shear wave elastography in detecting category 4a and 4b thyroid nodules.

Objectives: Differential diagnosis of benign and malignant thyroid imaging reporting and data system (TIRADS) category 4a and 4b nodules can be difficult using conventional ultrasonography (US). The objective of this study was to evaluate the diagnostic efficacy of a combination of the Chinese-TIRADS (C-TIRADS) and shear wave elastography (SWE) in detecting malignant nodules among category 4a and 4b thyroid nodules. Methods: Among 409 thyroid nodules in 332 patients that we included in this study, 106 thyroid nodules were diagnosed as category 4a and 4b using C-TIRADS. We used SWE to measure the maximum Young's modulus (Emax) values of category 4a and 4b thyroid nodules. We calculated the diagnostic efficacy of only the C-TIRADS, only SWE, and a combination of C-TIRADS with SWE, and compared these, while taking the pathology results as the gold standard. Results: The area under the ROC curve (AUC), sensitivity, and accuracy values of the combination of C-TIRADS and SWE (0.870, 83.3%, and 84.0%, respectively) were all higher when compared with the values of only the C-TIRADS (0.785, 68.5%, and 78.3%, respectively) or only SWE (0.775, 68.5%, and 77.4%, respectively) in the diagnosis of category 4a and 4b thyroid nodules. Conclusion: In this study, we found that the combination of C-TIRADS and SWE significantly improved the diagnostic efficacy in detecting malignant nodules among category 4a and 4b thyroid nodules, and this could provide a reference for further use of this combination by clinicians for diagnosis and treatment.

Mid-term follow-up surgical results in 284 cases of clival chordomas: the risk factors for outcome and tumor recurrence.

OBJECTIVE: Skull base chordoma (SBC) is rare and one of the most challenging diseases to treat. We aimed to assess the optimal timing of adjuvant radiation therapy (RT) and to evaluate the factors that influence resection and long-term outcomes. METHODS: In total, 284 patients with 382 surgeries were enrolled in this retrospective study. Postsurgically, 64 patients underwent RT before recurrence (pre-recurrence RT), and 47 patients underwent RT after recurrence. During the first attempt to achieve gross-total resection (GTR), when the entire tumor was resected, 268 patients were treated with an endoscopic midline approach, and 16 patients were treated with microscopic lateral approaches. Factors associated with the success of GTR were identified using χ2 and logistic regression analyses. Risk factors associated with chordoma-specific survival (CSS) and progression-free survival (PFS) were evaluated with the Cox proportional hazards model. RESULTS: In total, 74.6% of tumors were marginally resected [GTR (40.1%), near-total resection (34.5%)]. History of surgery, large tumor volumes, and tumor locations in the lower clivus were associated with a lower GTR rate. The mean follow-up period was 43.9 months. At the last follow-up, 181 (63.7%) patients were alive. RT history, histologic subtype (dedifferentiated and sarcomatoid), non-GTR, no postsurgical RT, and the presence of metastasis were associated with poorer CSS. Patients with pre-recurrence RT had the longest PFS and CSS, while patients without postsurgical RT had the worst outcome. CONCLUSION: GTR is the goal of initial surgical treatment. Pre-recurrence RT would improve outcome regardless of GTR.

Influence of lesion size on shear wave elastography in the diagnosis of benign and malignant thyroid nodules.

In shear wave elastography (SWE) studies, the optimal cutoff value of Young's modulus for the diagnosis of benign and malignant thyroid nodules varies greatly, which affects the clinical application of the method. The objective of this study was to evaluate the influence of thyroid nodule size on the clinical diagnostic efficacy of SWE. A total of 356 thyroid nodules of 280 patients were divided into three groups according to size (Group A: ≤ 1 cm; Group B: 1-2 cm; Group C: ≥ 2 cm). SWE was used to measure the maximum Young's modulus (Emax) values of all thyroid nodules. Receiver operating characteristic (ROC) curves were drawn with pathological results as the gold standard. For all nodules, the optimal cutoff value of Emax in SWE for diagnosing malignant thyroid nodules was 36.2 kPa. The sensitivity and specificity were 76.5% and 78.4%, respectively. Groups A, B, and C had different optimal Emax cutoff values of 33.7 kPa, 37.7 kPa, and 55.1 kPa, respectively. The area under the ROC curve (AUC) values of Groups A, B, and C (0.844, 0.886, and 0.935, respectively) were all greater than the values for all lesions (0.830). The specificity values of Groups A, B, and C (86.4%, 82.6%, and 88.2%, respectively) were all increased, and the sensitivity values of Groups B and C (89.7% and 96.4%, respectively) were also increased compared with the values for all lesions. Thyroid nodule size affects the optimal Emax cutoff value of SWE. We suggest that different cutoff values be used to diagnose benign and malignant thyroid nodules according to lesion size.

Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients: A Systematic Review and Network Meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of nonsurgical secondary prophylaxis interventions for esophageal varices (EV) rebleeding in cirrhotic patients using network meta-analysis. MATERIALS AND METHODS: Secondary prophylaxis of EV rebleeding in cirrhosis is searched on PubMed, Embase, and the Cochrane Library databases. The quality of literatures was extracted by 2 independent investigators according to the requirements of Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. Meta-analysis was performed on Review Manager 5.3 software for the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality; and STATA 15.1 software was used for network meta-analysis. RESULTS: In all, 57 randomized controlled trials were reviewed. Endoscopic band ligation (EBL)+argon plasma coagulation has not been recommended by guidelines, and it is rarely used; the number of existing studies and the sample size are small. Considering poor stability of the combined results, these studies were excluded; 55 literatures were included. In terms of reducing the incidence of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) surface under the cumulative ranking curve (SUCRA) (94.3%) was superior to EBL+endoscopic injection sclerotherapy (EIS) (84.4%), EIS+ß-blockers (77.9%), EBL (59.8%), EBL+ß-blockers+isosorbide-5-mononitrate (52.7%), EBL+ß-blockers (51.4%), EIS (34.2%), ß-blockers+isosorbide-5-mononitrate (23.7%), ß-blockers (20.8%), and placebo (0.8%). In reducing rebleeding-related mortality, TIPS SUCRA (87.2%) was more efficacious than EBL+EIS (83.5%), EIS (47.9%), EBL+ß-blockers (47.4%), ß-blockers (41.8%), EBL (34.5%), and placebo (7.6%). In reducing overall mortality, TIPS SUCRA (81.1%) was superior to EBL+EIS (68.9%), EIS+ß-blockers (59.2%), EBL+ß-blockers (55.4%), EIS (48.8%), EBL (48.7%), ß-blockers (34.2%), placebo (3.6%). CONCLUSIONS: TIPS was more effective in reducing the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality in cirrhosis. Combined with the above results, TIPS is more likely to be recommended as a secondary prophylaxis intervention for EV in cirrhosis.

Chinesization of the quality of life assessment, venous device-port, and its reliability and validity tests for patients with breast cancer.

OBJECTIVE: To translate the assessment item sets of the Canadian version of the quality of life assessment, venous device-port for breast cancer patients with chest and arm ports (i.e. different implanting sites) into Chinese version, and to conduct a test of reliability and validity for it. METHODS: According to the Brislin translation model, quality of life assessment, venous device-port underwent literal and back translations, and the Chinese version of quality of life assessment, venous device-port was preliminarily revised by consulting an expert and a preliminary test. A total of 270 cancer patients undergoing chemotherapy were assessed during the use of ports, and the reliability and the validity of the Chinese version of quality of life assessment, venous device-port scale were then tested. RESULTS: The scale consisted of 23 yes/no items and seven numerical rating scales. The total Cronbach's α coefficient of the scale was 0.829, and each item ranged from 0.812 to 0.845. The item-level content validity index was 0.67-1.00, and the scale-level content validity index/average and the scale-level content validity index/universal agreement were 0.98 and 0.90, respectively. The correlation coefficient of the repeated measurement results of the scale was 0.554 (p < 0.01). Exploratory factor analysis showed that the cumulative explained variance of five common factors was 64.197%. CONCLUSION: The Chinese version of quality of life assessment, venous device-port scale is an effective assessment tool for quality of life with good reliability and validity in breast cancer patients with different implantation sites for totally implanted venous access devices in northern China.

Multiplier method estimates of the population of men who have sex with men: the effect of privacy protection.

OBJECTIVES: The stigmatization of men who have sex with men (MSM) has led to an underestimation of their population size. To address this, the United Nations Programme on HIV/Acquired Immunodeficiency Syndrome and World Health Organization developed a multiplier method. However, nearly all multiplier method estimates of MSM population size in China are far below national estimates. This study explores how privacy protection to address and avoid MSM stigmatization can affect reliable estimates. METHODS: Data from an MSM website, a bar, and a peer-based HIV testing were used to produce three multiplier method estimates of the MSM population size in Taiyuan, China, in 2014. The effect of privacy protection on stigmatization was explored by comparing the peer-based HIV testing with other estimates. We used a national estimate as a reference to verify potential underestimation. RESULTS: The website and bar estimates were 5- to 10-times and 8- to 16-times lower than the Chinese national estimate range, respectively. Conversely, the peer-based HIV testing estimate was within the national estimate range. CONCLUSIONS: Though the multiplier method was developed to estimate the size of stigmatized populations, it might be affected by privacy protection addressing stigmatization; this should be considered when gathering data.

Identification of a prognostic 28-gene expression signature for gastric cancer with lymphatic metastasis.

Gastric cancer (GC) patients have high mortality due to late-stage diagnosis, which is closely associated with lymph node metastasis. Exploring the molecular mechanisms of lymphatic metastasis may inform the research into early diagnostics of GC. In the present study, we obtained RNA-Seq data from The Cancer Genome Altas and used Limma package to identify differentially expressed genes (DEGs) between lymphatic metastases and non-lymphatic metastases in GC tissues. Then, we used an elastic net-regularized COX proportional hazard model for gene selection from the DEGs and constructed a regression model composed of 28-gene signatures. Furthermore, we assessed the prognostic performance of the 28-gene signature by analyzing the receive operating characteristic curves. In addition, we selected the gene PELI2 amongst 28 genes and assessed the roles of this gene in GC cells. The good prognostic performance of the 28-gene signature was confirmed in the testing set, which was also validated by GSE66229 dataset. In addition, the biological experiments showed that PELI2 could promote the growth and metastasis of GC cells by regulating vascular endothelial growth factor C. Our study indicates that the identified 28-gene signature could be considered as a sensitive predictive tool for lymphatic metastasis in GC.

Incidence and severity of sexual dysfunction among women with breast cancer: a meta-analysis based on female sexual function index.

PURPOSE: Previous meta-analyses have examined the prevalence of sexual dysfunction among women with cancer, but there is no breast cancer (BC)-specific study. We therefore conducted a meta-analysis to examine the prevalence and severity of female sexual dysfunction (FSD) in women with BC. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, WanFang Data, and VIP for relevant studies published between April 2000 and January 2017. Data were extracted from studies which assessed FSD prevalence and sexual function in women with BC using the female sexual function index (FSFI). Meta-analyses were performed by pooling the prevalence rates of FSD and total FSFI scores. Meta regression was performed to explore the sources of heterogeneity. RESULTS: We selected 19 published studies involving a total of 2684 women with BC. In this study population, overall FSD prevalence was 73.4% (95% confidence interval (CI) 64.0%, 82.8%), and the total FSFI score was 19.28 (95% CI 17.39, 21.16). Among Asian, American, and European women with BC, there were significant differences in FSD prevalence (P < 0.001), and there was marginally significant difference (P = 0.07) in sexual function between these groups. There was also a marginally significant difference between individuals from mainland China and from other countries in FSD prevalence (P = 0.06) and FSFI score (P = 0.07). CONCLUSIONS: Overall, women with BC have high FSD prevalence and low sexual function. American women with BC have a higher average FSD prevalence and lower average sexual function than Asian women with BC. The FSD prevalence in women with BC in mainland China was slightly higher than in other countries.

Fabrication of oxidase-like polyaniline-MnO2 hybrid nanowires and their sensitive colorimetric detection of sulfite and ascorbic acid.

Recently, nanomaterials-based oxidase-like artificial enzymes have attracted much attention due to their unique catalytic efficiency, high environmental stability and low-cost. In this study, we for the first time show the application of polyaniline (PANi)-MnO2 hybrid nanowires for oxidase mimicking. The PANi-MnO2 hybrid nanowires are prepared via a redox reaction between PANi nanowires and KMnO4. The as-prepared PANi-MnO2 hybrid nanowires exhibit an enhanced oxidase-like catalytic activity compared with individual PANi nanowires and MnO2 alone due to the synergistic catalytic effect between the two components. Based on the above findings, we construct PANi-MnO2 hybrid nanowires-based colorimetric assay for sensitive and selective detection of sulfite and ascorbic acid (AA). The detection limits of sulfite and AA are as low as 79 and 26 nM, respectively, which is much lower than many previous reported enzyme mimics-based colorimetric sensors. This work demonstrates a broad potential prospect of PANi-MnO2 hybrid nanowires in biotechnology, environmental science and food safety.

The effect of Baduanjin qigong combined with CBT on physical fitness and psychological health of elderly housebound.

BACKGROUND: To investigate the effectiveness of Baduanjin qigong combined with cognitive-behavior therapy (CBT) on the physical fitness and psychological health of elderly housebound. MATERIALS AND METHODS: The 120 elderly housebound were randomly divided into 3 intervention groups: Baduanjin training, Baduanjin training combined with CBT, and CBT. The interventions were conducted by means of home visits over 6 months. Spirometry, SF-36 health survey of quality of life, and Lawton and Brody Instrumental Activities of Daily Living Scale (IADL) were used to collect physical health data, and self-evaluation of overall health status, self-evaluation of loneliness, and short-form geriatric depression scale (GDS-15) were used to collect mental health data at baseline, 3 months, and 6 months after intervention. Data was analyzed by repeated measures analysis of variance (rANOVA) and chi-squared test (χ test). RESULTS: Forced vital capacity (FVC), maximum voluntary ventilation (MVV), quality of life (QOL), and self-reported health status were significantly increased (P < .05) in the group receiving joint Baduanjin and CBT intervention at 3 months and 6 months, as compared to the Baduanjin only group or the CBT only group. Activities of daily living (ADL), self-evaluated loneliness, and level of depression were significantly lowered (P < .05) in the group receiving joint Baduanjin and CBT intervention at 3 months and 6 months, as compared to the Baduanjin only group or the CBT only group. CONCLUSIONS: Physical and psychological statuses of elderly housebound were significantly improved by Baduanjin training combined with CBT. The effect of the combined intervention exceeded that of CBT or Baduanjin alone.

Fabrication of ternary MoS2-polypyrrole-Pd nanotubes as peroxidase mimics with a synergistic effect and their sensitive colorimetric detection of l-cysteine.

Over the past few years, nanomaterials-based enzymatic mimics have attracted tremendous attention due to their excellent catalytic activity and environmental stability. In this work, ternary MoS2-polypyrrole (PPy)-Pd nanotubes have been prepared through a hydrothermal reaction and in situ redox polymerization process between pyrrole monomer and Na2PdCl4. The prepared MoS2-PPy-Pd nanotubes exhibited a higher peroxidase-like catalytic activity than individual MoS2, MoS2-PPy, PPy-Pd and MoS2-Pd nanocomposites due to the synergistic catalytic effect between the three components. The catalytic kinetic of MoS2-PPy-Pd nanotubes follows Michaelis-Menten behaviors, exhibiting a good affinity to both 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 substrates. On the basis of high peroxidase-like catalytic efficiency of the MoS2-PPy-Pd nanotubes, a simple and convenient colorimetric strategy for the rapid and sensitive detection of l-cysteine with a detection limit of 0.08 µM has been developed. In addition, a high selectivity towards the detection of l-cysteine is achieved. This work present an opportunity of the prepared ternary MoS2-PPy-Pd nanotubes for promising potential applications in biosensing, environmental monitoring, and medical diagnostics.

Development of a Quality of Sexual Life Questionnaire for Breast Cancer Survivors in Mainland China.

BACKGROUND There is a great need for a quality of sexual life questionnaire (QVS) in breast cancer survivors (BCSs) based on the Chinese social culture since the imported tools lack localization verification. To develop a QVS in BCSs and determine its validity and reliability. MATERIAL AND METHODS In the qualitative study, a total of 21 BCSs were interviewed by purposive sampling and snowball sampling; and in the quantitative study, a total of 249 BCSs, who were admitted and received outpatient follow-up, were investigated. Regarding construct validity, factor analysis was performed. The female sexual function index (FSFI), self-rating depression scale (SDS), and Locke-Wallace marital adjustment test (LWMAT) were used to evaluate criterion validity. Cronbach's alpha coefficient was used as an index of internal consistency. To evaluate test-retest reliability, 50 patients were re-evaluated after 1 week. RESULTS We put 28 items in the factor analysis model: (1) 5 factors were extracted by exploratory factor analysis (EFA), with a cumulative contribution of 60.37%; (2) the confirmatory factor analysis (CFA) showed that the path coefficients among the factors were all above 0.5, and the standardized load coefficients of the most items were above 0.5; (3) the Cronbach's alpha coefficient was 0.929 for the overall questionnaire, and ranged from 0.571 to 0.869 for the 5 factors; (4) the correlation coefficients between the overall questionnaire and the FSFI, SDS, and LWMAT were 0.582, -0.456 and 0.515, respectively (P<0.01); and (5) the test-retest correlation coefficient was 0.816, and the split-half-reliability coefficient was 0.899. CONCLUSIONS The QVS in BCSs has good reliability and validity, and can be used to assess the quality of sexual life among BCSs in Mainland China.

One-step in situ growth of ZnS nanoparticles on reduced graphene oxides and their improved lithium storage performance using sodium carboxymethyl cellulose binder.

ZnS nanoparticles are in situ grown on reduced graphene oxides (rGO) via a simplified one-step hydrothermal method. Sodium carboxymethyl cellulose (CMC) is firstly applied as the binder for ZnS based anodes and shows a more advantageous binding effect than PVDF. To simplify the synthesis procedure, l-cysteine is added as the sulfur source for ZnS and simultaneously as the reducing agent for rGO. The average diameter of ZnS nanoparticles is measured to be 13.4 nm, and they uniformly disperse on the rGO sheets without any obvious aggregation. As anode materials, the CMC bound ZnS-rGO nanocomposites can maintain a high discharge capacity of 705 mA h g-1 at a current density of 500 mA g-1 for 150 cycles. The significantly improved electrochemical performance mainly derives from the combined effects of the small and uniformly dispersed ZnS nanoparticles, the high conductivity and structural flexibility of rGO and the strong binding ability of CMC.

Occurrence of and factors influencing elderly homebound in Chinese urban community: A cross-sectional study.

Studies on the occurrence of homebound and the factors influencing it are available. However, the study of community homebound in China is still in its preliminary stage. No previous studies about this issue are available. This study aims to assess the occurrence of and factors influencing homebound elderly in Chinese communities and to provide a basis for effective intervention and prevention of homebound elderly people.One sample community from three provinces was randomly selected. Investigations were performed on the selected communities and 2180 elderly people were chosen as the research subjects. Unified survey scales were used. Home visit and face-to-face interviews were performed to ensure that no single qualified survey respondent was missed.The rate of morbidity in homebound elderly Chinese community was found to be 15.49% and it gradually increased with age, and also with a lower education or poorer Activities of Daily Living (ADL). Single factor analysis showed that general situation, living habits, physical condition, mental condition, society, social support, and other factors affected the occurrence of community homebound elderly. Women were more likely to be homebound than men (P < .05). Having a spouse or high income reduced the rate of morbidity in the homebound elderly (P < .05). Multifactor regression analysis revealed that poor ADL, depression, hearing impairment, being old, no exercise, and low social support are the main influencing factors.Appropriate measures should be taken based on the specific influencing factor to prevent the occurrence of homebound.

Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury.

OBJECTIVE: This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R) injury via glycogen synthase kinase 3ß (GSK-3ß) and the mitochondrial permeability transition pore (mPTP) through inhibition of endoplasmic reticulum stress (ERS). METHODS AND RESULTS: H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3ß phosphorylation and GRP94 expression. NECA increased GSK-3ß phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3ß and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3ß phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3ß and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. CONCLUSION: These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3ß via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3ß inactivation by NECA.

Apolipoprotein E mimetic peptide protects against diffuse brain injury.

Apolipoprotein E plays a crucial role in inhibiting chronic neurodegenerative processes. However, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein E mimetic peptide on diffuse brain injury. Apolipoprotein E mimetic peptide was administered into the caudal vein of rats with diffuse brain injury before and after injury. We found that apolipoprotein E mimetic peptide significantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental findings demonstrate that apolipoprotein E mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mitochondrial apoptotic pathway.

Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia.

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and accelerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

Targeted knockdown of IQGAP1 inhibits the progression of esophageal squamous cell carcinoma in vitro and in vivo.

IQGAP1 is a scaffolding protein that can regulate several distinct signaling pathways. The accumulating evidence has demonstrated that IQGAP1 plays an important role in tumorigenesis and tumor progression. However, the function of IQGAP1 in esophageal squamous cell carcinoma (ESCC) has not been thoroughly investigated. In the present study, we showed that IQGAP1 was overexpressed in ESCC tumor tissues, and its overexpression was correlated with the invasion depth of ESCC. Importantly, by using RNA interference (RNAi) technology we successfully silenced IQGAP1 gene in two ESCC cell lines, EC9706 and KYSE150, and for the first time found that suppressing IQGAP1 expression not only obviously reduced the tumor cell growth, migration and invasion in vitro but also markedly inhibited the tumor growth, invasion, lymph node and lung metastasis in xenograft mice. Furthermore, Knockdown of IQGAP1 expression in ESCC cell lines led to a reversion of epithelial to mesenchymal transition (EMT) progress. These results suggest that IQGAP1 plays crucial roles in regulating ESCC occurrence and progression. IQGAP1 silencing may therefore develop into a promising novel anticancer therapy.