The association between paced left ventricular activation time and cardiac reverse remodeling in heart failure patients with left bundle branch block.

INTRODUCTION: The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow-up. METHODS: Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT-proBNP and echocardiographic parameters were recorded during routine follow-up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow-up were analyzed. RESULTS: Eighty-three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT-proBNP 1057[513-3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p < .001) and median paced LVAT was 80[72-88] ms. After a median follow-up of 12[9-29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT-proBNP decreased to 215[73-532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p < .001; LVEFbaseline: p = .001). The difference in LVEF6M was statistically significant among groups (p < .001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p = .090). There was no significant correlation between ΔLVEF6M-baseline, ΔLVEF1Y-6M and LVAT respectively (ΔLVEF6M-baseline: p = .261, r = -.126; ΔLVEF1Y-6M: p = .085, r = .218). CONCLUSION: Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover.

An Evidence-Based Medical Review on Promoting Gastrointestinal Function Recovery After Colorectal Cancer Surgery.

Objective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC. Methods: Based on the hierarchical "6S" evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria. Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management. Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.

Polymorphisms of TRIB1 genes for coronary artery disease and stroke risk: A systematic review and meta-analysis.

BACKGROUND AND AIMS: In recent years, the results of the association between Tribbles Pseudokinase 1 (TRIB1) gene polymorphism and the risk of coronary artery disease (CAD) and stroke are inconsistent. This study aimed to systematically review the literature on TRIB1 gene polymorphisms and susceptibility to coronary atherosclerotic heart disease (CAD) and stroke. METHODS: This study collected studies published until May 2022 through a systematic search of PubMed, Web of Science, and Google Scholar databases. After a systematic literature search, pooled odds ratio (OR) and their corresponding 95 % confidence interval (CI) were used to assess the strength of the association. RESULTS: We identified 6 studies on rs17321515, including 12,892 controls and 4583 patients, and 3 on rs2954029, including 1732 controls and 1305 patients. In different genetic models, the rs2954029 genetic polymorphism significantly increased the risk of CAD and stroke. In the codominant model, the AA genotype increased the risk of CAD and stroke (OR = 1.74, 95 % CI = 1.39-2.17, P < 0.001); the TA genotype also increased the prevalence of CAD and stroke risk (OR = 1.39, 95 % CI = 1.18-1.64, P < 0.001). Compared with the control group, the TT + TA genotype increased the risk of CAD and stroke in the dominant genetic model (OR = 1.46, 95 %CI = 1.25-1.71, P < 0.001), and in the recessive model, the TA + AA genotype increased the risk of CAD and stroke (OR = 1.41, 95 % CI = 1.15-1.72, P < 0.001). In addition, the TRIB1 rs17321515 polymorphism was not found to be associated with the risk of CAD and stroke, which may be related to other factors such as race. CONCLUSIONS: The rs2954029 A allele was significantly associated with an increased risk of CAD and stroke, according to the present meta-analysis. However, the association of rs17321515 polymorphism with susceptibility to CAD and stroke has not been found in this study.

Cardiac resynchronization therapy for patients with heart failure and nonspecific intraventricular conduction delay.

The efficacy of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) is well established with Class I or IIa recommendation according to 2021 ESC Guidelines on cardiac pacing and CRT, whereas non-LBBB morphology is less recommended. There is insufficient evidence that proves patients with NICD could benefit from CRT. As patients with NICD are characterized by heterogeneity, the effect of CRT on these patients is still controversial. Although the proportion of NICD in the population is lower than that of LBBB patients, it is still worth investigating the effects of CRT on patients with NICD in an era of His-Purkinje conduction system pacing (HPCSP).

A new model for predicting the occurrence of polycystic ovary syndrome: Based on data of tongue and pulse.

Background and objective: Polycystic ovary syndrome is one of the most common types of endocrine and metabolic diseases in women of reproductive age that needs to be screened early and assessed non-invasively. The objective of the current study was to develop prediction models for polycystic ovary syndrome based on data of tongue and pulse using machine learning techniques. Methods: A dataset of 285 polycystic ovary syndrome patients and 201 healthy women were investigated to identify the significant tongue and pulse parameters for predicting polycystic ovary syndrome. In this study, feature selection was performed using least absolute shrinkage and selection operator regression. Several machine learning algorithms (multilayer perceptron classifier, eXtreme gradient boosting classifier, and support vector machine) were used to construct the classification models to predict the presence of polycystic ovary syndrome. Results: TB-L, TB-a, TB-b, TC-L, TC-a, h3, and h4/h1 in tongue and pulse parameters were statistically associated with polycystic ovary syndrome presence. Among the several machine learning techniques, the support vector machine model was optimal for the comprehensive evaluation of this dataset and deduced the area under the receiver operating characteristic curve, DeLong test, calibration curve, and decision curve analysis. Conclusion: The machine learning model with tongue and pulse factors can predict the existence of polycystic ovary syndrome precisely.

Real-world application of a fast stool DNA test for colorectal cancer screening in primary screening positive population.

BACKGROUND: Stool DNA test has been emerged as an effective noninvasive method for colorectal cancer (CRC) screening, but the real-world performance of stool DNA test in Chinese population has rarely been reported. METHODS: A total of 36,527 subjects were recruited in Haining City from January 2021 to December 2021. Participants underwent primary screening by taking both two-samples fecal immunochemical tests (FITs) and high-risk factor questionnaire (HRFQ), and those who tested either positive by FITs or evaluated to be high risk by HRFQ were recommended to undertake subsequent stool DNA test and colonoscopy. RESULTS: Of 36,527 participants, 34,778 (95%) completed both HRFQ and FITs, 9947 (29%) showed positive results during primary screening, and the colonoscopy compliance rate was 49%. Of primary screening positives, 8733 (88%) completed stool sample collections, and colonoscopy results from 4293 eligible participants were used for analyzing the performance of stool DNA test. The sensitivities for detecting CRC and advanced adenomas (AA) were 100% (95% CI: 60-100%) and 40% (95% CI: 34-46%), and the area under curve (AUC) was 0.961 (95% CI:0.954-0.967) and 0.625 (95% CI: 0.609-0.641), respectively. The specificity of stool DNA test was 84% (95% CI: 82-85%). The false-positive rate for stool DNA test is about 10% less than that of primary screening. CONCLUSION: Stool DNA test is a cost-effective and promising alternative strategy for CRC screening in China.

Parameter study on characteristic pulse diagram of polycystic ovary syndrome based on logistic regression analysis.

This study aimed to explore the parameters of the independent predictive characteristic pulse diagram of polycystic ovary syndrome (PCOS) by analysing the pulse characteristics between healthy women and the PCOS group. A total of 278 women were recruited for this study. Pulse wave parameters were collected by the pulse spectrum analyser. The single-factor analysis of the pulse diagram parameters was used to identify significant indicators, and the logistic regression analysis was carried out on the above indicators with statistical differences to obtain independent predictors. According to the single-factor and multi-factor analyses, h1, h5, h3/h1, t, t1 and t5 were independent predictors of PCOS diagnosis. The results showed that PCOS patients had a faster heart rate, decreased left ventricular systolic function and decreased aortic compliance compared to healthy individuals. These findings suggested that the characteristic pulse parameters screened out are valuable for the diagnosis of PCOS.IMPACT STATEMENTWhat is already known on this subject? Polycystic ovary syndrome (PCOS) is a common gynecological reproductive endocrine and metabolic disease, which is significant for screening and early intervention in the disease. However, due to the lack of pulse's diagnostic evidence of PCOS, there is still an unknown area in the research on the correlation between PCOS and pulse diagram parameters.What do the results of this study add? This study fills the gap between the research on PCOS and pulse wave. The study also shows that the pulse characteristic parameters h1, h5, h3/h1, t, t1, and t5 are independent predictors of PCOS, suggesting that the patients have a higher heart rate, lower ventricular systolic function, and aortic compliance than healthy individuals.What are the implications of these findings for clinical practice and/or further research? Prominent risk factors for pulse parameters associated with the occurrence of PCOS facilitate early screening and diagnosis of the disease. The objectification of pulse diagnosis helps to establish a health management model, which can be used for the accurate assessment and treatment of PCOS by traditional Chinese medicine (TCM). It provides a clinical reference for the study of pulse diagnosis objectification.

One-sample quantitative and two-sample qualitative faecal immunochemical tests for colorectal cancer screening: a cross-sectional study in China.

OBJECTIVES: Quantitative faecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening in the Western countries, whereas qualitative FITs are preferred in China. The present study aimed to compare the screening yield between one-sample quantitative FIT and two-sample qualitative FIT for CRC screening. DESIGN: A cross-sectional study. SETTING: A population-based CRC screening programme was conducted in 28 communities in Haining City, Zhejiang Province, China. PARTICIPANTS: Consecutive participants aged 40-74 years were invited to undergo the CRC screening programme. Two-sample qualitative FITs were offered between January 2019 and December 2019, and one-sample quantitative FIT was offered between August 2019 and February 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were detection rates of advanced neoplasms, including CRCs and advanced adenomas. Secondary outcomes were positivity rates and colonoscopy resource demand for the two FITs. The positivity thresholds were 20 µg and 1-5 µg haemoglobin per gram of faeces for the quantitative and qualitative FITs, respectively. RESULTS: A total of 19 131 and 28 804 invitees were assigned to the two-sample qualitative and one-sample quantitative groups, respectively. Positivity rates were 14.2% for the two-sample qualitative FIT and 5.4% for the one-sample quantitative FIT. Detection rates of advanced colorectal neoplasms at colonoscopy using one-sample quantitative FIT and two-sample qualitative FIT were 17.6% (95% CI: 14.6% to 20.6%) and 10.5% (95% CI: 8.7% to 12.4%), respectively. Both detection rates of cancer and advanced adenoma were higher in the one-sample quantitative FIT group than those in the two-sample qualitative FIT group. Moreover, one-sample quantitative FIT significantly reduced the colonoscopy load for detection of one advanced neoplasm case (5, 95% CI: 5 to 7) than the two-sample qualitative FIT (10, 95% CI: 8 to 11). CONCLUSIONS: The one-sample quantitative FIT for CRC screening increases the detection rate of advanced neoplasia and reduces the colonoscopy workload compared with the two-sample qualitative FIT.

Risk of proximal femoral nail antirotation (PFNA) implant failure upon different lateral femoral wall thickness in intertrochanteric fracture: a finite element analysis.

Proximal Femoral Nail Antirotation (PFNA) has been commonly used to treat intertrochanteric fractures, despite the risk of implant failure. The integrity of the femur could influence the risk of implant failure. This study evaluated the influence of lateral femoral wall thickness on the potential of implant failure. A finite element model of the hip was reconstructed from the Computed Tomography of a female patient. Five intertrochanteric fracture models at different lateral femoral wall thickness (T1 = 27.6 mm, T2 = 25.4 mm, T3 = 23.4 mm, T4 = 21.4 mm, and T5 = 19.3 mm) were then created and fixed with PFNA. We simulated a critical loading condition by a high loading case during walking. Elastoplastic material models with yield stress and failure strain were applied to the bone and implant in which breakage can be simulated using the element deletion function. In addition, the stress and displacement of the implant and femur were analysed. Implant breakage occurred at the sides of the proximal nail canal in cases of T4 and T5 which was further supported by the higher maximum von Mises stress and nail displacement. The increased stress and displacement of the implant may implicate a reduction of stability and risk of implant failure. We suggested that precaution shall be taken when the wall thickness was less than 21.4 mm.

Cement augmentation of the proximal femoral nail antirotation for the treatment of two intertrochanteric fractures - a comparative finite element study.

BACKGROUND: There are concerns regarding initial stability and cutout effect in proximal femoral nail antirotation (PFNA) treating intertrochanteric fractures. No study have used finite element analysis (FEA) to investigate the biomechanics. This study aimed to compare the cutout effect, stress and displacement between stable (AO31-A1.3) and unstable (AO31-A2.2) intertrochanteric fractures treated by cement augmented PFNA. METHODS: Four femoral finite element models (FEMs) were constructed and tested under the maximum loading during walking. Non-augmented and augmented PFNA in two different intertrochanteric fractures were respectively simulated, assuming Tip Apex Distance (TAD) < 25 mm within each FEM. The cutout effect, stress and displacement between femur and PFNA were compared in each condition. RESULTS: Cutout effect was observed in both non-augmented femoral head and was more apparently in unstable intertrochanteric fracture model. After reinforced by bone cement, no cutout effect occurred in two models. Stress concentration were observed on medial part of intertrochanteric region and the proximal part of helical blade before augmented while were observed on femoral shaft and the conjunction between blade and nail after augmented in both FEMs. Displacement mainly appeared on femoral head and the helical blade tip before augmented while distributed moderately on intertrochanteric region and the upper part of nail after augmented in both FEMs. The maximum stress and displacement value of femur decreased both in stable and unstable model after augmented but was more significantly in the unstable one. The maximum stress and displacement value of PFNA increased both in stable and unstable model after augmented but was more significantly in the unstable one. CONCLUSION: Our FEA study indicated that the cement augmentation of the PFNA biomechanically enhances the cutout resistance in intertrochanteric fracture, this procedure is especially efficient for the unstable intertrochanteric fracture.

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening: A cross-sectional population-based analysis.

OBJECTIVE: Integration of risk stratification into fecal immunochemical test (FIT) might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer (CRC) screening. A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment (QRA) and FIT, FIT-only and QRA-only strategies in a CRC screening program in China. METHODS: The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China. Participants were first invited to undertake QRA and one-time FIT (OC-sensor). Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy. Participation, detection rate, and resource demand for colonoscopy were calculated and compared. RESULTS: Of the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 completed the FIT-only strategy. For the parallel combination, FIT-only, and QRA-only strategies, the overall positivity rates were 10.2% (2,928/28,806), 5.4% (1,096/20,214), and 6.8% (1,944/28,795), respectively; the yield of advanced neoplasm per 10,000 invitees were 46.9 [95% confidence interval (95% CI): 39.8-55.4], 36.8 (95% CI: 30.5-44.4), and 12.2 (95% CI: 8.8-16.8), respectively; the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7% (95% CI: 4.0%-5.6%), 9.9% (95% CI: 8.3%-11.9%), and 1.9% (95% CI: 1.3%-2.6%), respectively; the number of colonoscopies required to detect one advanced neoplasm was 11.4 (95% CI: 9.8-13.4), 5.7 (95% CI: 4.8-6.7), and 28.4 (95% CI: 20.7-39.2), respectively. CONCLUSIONS: The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

[Finite element analysis of different intramedullary fixation methods for the treatment of senile pubic ramus fractures].

OBJECTIVE: To evaluate the biomechanical stability of elastic intramedullary nail in the treatment of pubic ramus fractures by finite element analysis, and to compare the stability of elastic intramedullary nail with cannulated screw intramedullary fixation. METHODS: The CT data of the pelvis of a volunteer were selected, and the three-dimensional model of the pelvis was reconstructed by reverse engineering software and the fracture of the pubic ramus fractures was simulated by osteotomy. The hollow nail model, single elastic nail model and double elastic nailmodel were assembled with different implants respectively. The mesh division, material assignment loading and other steps were carried out in the ANSYS software, and then the calculation was submitted. RESULTS: The overall displacement of the pelvis of the elastic nail model was smaller than that of the cannulated screw model, in which the double elastic nail model had the smallest overall displacement, but the cannulated screw model had the smallest plant displacement and the single elastic nail model had the largest plant displacement. Although the stress of cannulated screw was small, there was obvious stress concentration, the stress of elastic nail was large, but there was no obvious stress concentration, especially the stress distribution of double elastic nail was more uniform and the overall stress of pelvis was the smallest. CONCLUSION: All the three fixation methods can effectively improve the stability of the anterior ring of the pelvis. Among them, there is no significant difference in the overall biomechanical propertiesof hollow nail fixation and double elastic nail fixation, which is better than that of single elastic nail fixation. Elastic nail fixation has the advantages of minimally invasive surgery and good biomechanical stability, so it can be used as a better surgical method for the treatment of pubic ramus fractures.

The role of low molecular weight heparin on recurrent pregnancy loss: A systematic review and meta-analysis.

To assess the roles of the low molecular weight heparin (LMWH) on recurrent pregnancy loss (RPL). The relevant studies of all randomized controlled trials (RCTs) were retrieved, and the systematic evaluation was conducted. PubMed, Embase, and Cochrane library databases were searched by using keywords, including low-molecular-weight heparin or LMWH, and recurrent miscarriage or recurrent pregnancy loss in pregnant women from their earliest data to February 2020. Two investigators independently evaluated eligibility. Risk ratios (RRs) and their corresponding 95% confidence interval (CI) were determined. To pool the results, this meta-analysis was performed using random-effect model due to the high heterogeneity among these eight studies. A total of eight RCTs involving 1854 participants were included in the meta-analysis involving 963 patients with RPL who were prescribed LMWH (enoxaparin, tinzaparin, or dalteparin) alone and 891 patients who were treated with no LMWH interventions (placebo, folic acid or non-treatment) were compared. Pooled data from the remaining eight RCTs showed the differences between intervention groups and control groups. Compared with control groups, LMWH had significantly improved live births (RR,1.19; 95%CI, 1.03 to 1.38; P = 0.02), and reduced miscarriage rates (RR, 0.62; 95%CI, 0.43 to 0.91; P = 0.01). The study suggested that LMWH could improve the live births and reduce the miscarriage rates of RPL. Therefore, LMWH might be a good treatment choice for women with unexplained PRL.

Characterisation of hexagonal birnessite with a new and rapid synthesis method-comparison with traditional synthesis.

Birnessite is one of the most important manganese oxides that can control the geochemical behaviors of pollutants or can be applied to form industrial products. Many studies have been conducted on the synthesis of hexagonal birnessite because different synthesis methods can affect the structural, morphological, and physicochemical properties of hexagonal birnessite. However, there are still some defects in these synthesis methods. Therefore, a new synthesis method that is rapid, simple, and low-cost was proposed in this study involving the reduction of KMnO4 by H2O2 in a H2SO4 solution without controlling the pH, temperature and pressure. Using a series of XRD, chemical composition, AOS, SSA, SEM, FTIR, and TGA analyses, Bir-H2O2 was found to have lower crystallinity than Bir-HCl. However, the AOS and SSA of Bir-H2O2 were 3.87 and 103 m2 g-1 higher than those of Bir-HCl, i.e., 3.70 and 22 m2 g-1, respectively. Moreover, both Bir-H2O2 and Bir-HCl had similar particle morphology and thermal stability; in addition, the maximum adsorption content of Pb2+ on Bir-H2O2 (∼3006 mmol kg-1) was ∼30% greater than that on Bir-HCl (∼2285 mmol kg-1) at pH 5.5; this indicated that the adsorption of Pb2+ on Bir-H2O2 was better and belonged to a pseudo-second-order model. All the abovementioned results indicate that Bir-H2O2 synthesized herein using the proposed synthesis method can have large application value.

Molecular Mapping of Reduced Plant Height Gene Rht24 in Bread Wheat.

Height is an important trait related to plant architecture and yield potential in bread wheat (Triticum aestivum L.). We previously identified a major quantitative trait locus QPH.caas-6A flanked by simple sequence repeat markers Xbarc103 and Xwmc256 that reduced height by 8.0-10.4%. Here QPH.caas-6A, designated as Rht24, was confirmed using recombinant inbred lines (RILs) derived from a Jingdong 8/Aikang 58 cross. The target sequences of Xbarc103 and Xwmc256 were used as queries to BLAST against International Wheat Genome Sequence Consortium database and hit a super scaffold of approximately 208 Mb. Based on gene annotation of the scaffold, three gene-specific markers were developed to genotype the RILs, and Rht24 was narrowed to a 1.85 cM interval between TaAP2 and TaFAR. In addition, three single nucleotide polymorphism (SNP) markers linked to Rht24 were identified from SNP chip-based screening in combination with bulked segregant analysis. The allelic efficacy of Rht24 was validated in 242 elite wheat varieties using TaAP2 and TaFAR markers. These showed a significant association between genotypes and plant height. Rht24 reduced plant height by an average of 6.0-7.9 cm across environments and were significantly associated with an increased TGW of 2.0-3.4 g. The findings indicate that Rht24 is a common dwarfing gene in wheat breeding, and TaAP2 and TaFAR can be used for marker-assisted selection.

The regulation of SKF38393 on the signaling pathway of dopamine D1 receptor in hippocampus during chronic sleep deprivation.

BACKGROUND: Hippocampal functions are sensitive to sleep deficiency. Dopamine D1 receptor (D1R) in hippocampus can regulate the expression of cAMP response element binding protein (CREB) through PKA, MAPK and phosphoinositide pathway, but which pathway plays the major role in hippocampus during Chronic sleep deprivation (CSD) is unclear. METHODS: The CSD model was created, SKF rats were administered the D1R agonist (SKF38363), and hippocampus from each animal was dissected for following molecular detection. The gene and protein levels of CREB and key molecules in D1R pathways were measured by real-time PCR and western blotting, respectively. RESULTS: Both the gene and protein expression of CREB in hippocampus decreased by CSD and improved significantly by SKF38393 (p<0.05). Both the gene and protein expression of PKA in hippocampus decreased by CSD and improved significantly by SKF38393 (p<0.05). SKF38393 just significantly improved the gene level of CaMK IV and the protein level of p-CaMK IV (p<0.05) in CSD rats, but it cannot improve the protein expression of ERK1/2 and p-ERK1/2. DISCUSSION: CSD significantly decreased the expression of CREB in hippocampus. As the key molecules, PKA and CaMK IV play an important role during the improvement of hippocampus by the activation of D1R, and this process might be improved during CSD through the PKA and phosphoinositide pathway.

Mangiferin inhibits lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling.

OBJECTIVE: Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms. DESIGN: The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits. RESULTS: We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-κB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment. CONCLUSIONS: Mangiferin decreases LPS-induced production of IL-6 in human oral epithelial cells by suppressing TLR signaling, and this glucosylxanthone may have potential for the treatment of periodontitis.

Co-culture of bone marrow stem cells and macrophages indicates intermediate mechanism between local inflammation and innate immune system in diabetic periodontitis.

Diabetic periodontitis (DP), which has been shown to cause alveolar bone loss, is among the most common complications associated with diabetes. The precise mechanisms underlying alveolar bone loss in patients with DP remain unclear. Therefore, the present study established a co-culture system of bone marrow stem cells (BMSCs) and macrophages, in order to investigate the potential mechanisms underlying DP-associated alveolar bone loss in vitro. In addition, Porphyromonas gingivalis (PG) periodontal infection and high glucose levels were used to induce DP in mice. The present study evaluated the protein expression levels of various chemokines and the migration of BMSCs and macrophages. The protein expression levels of extracellular signal-regulated kinase 1 and 2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK) were significantly increased in the BMSCs exposed to high glucose and PG, which may have been due to the activation of MAPK. In addition, DP induction in mice was associated with the release of chemokine (C-C motif) ligand 2 (CCL2) from BMSCs and the secretion of chemokine (C-C Motif) receptor 2 (CCR2) and tumor necrosis factor-α from macrophages, which was associated in turn with enhanced adhesion and chemotaxis of macrophages. The results of the present study suggested that DP led to the upregulation of CCL2 in the periodontal tissues and enhanced macrophage infiltration via the CCL2/CCR2 axis, which in turn promoted alveolar bone loss.

Influence of SKF38393 on changes of gene profile in rat prefrontal cortex during chronic paradoxical sleep deprivation.

Chronic paradoxical sleep deprivation (CSD) can induce dramatic physiological and neurofunctional changes in rats, including decreased body weight, reduced learning and memory, and declined locomotor function. SKF38393, a dopamine D1 receptor agonist, can reverse the above damages. However, the mechanism of CSD syndrome and reversal role of SKF38393 remains largely unexplained. To preliminarily elucidate the mechanism of the neural dysfunction caused by CSD, in the present study we use gene chips to examine the expression profile of more than 28,000 transcripts in the prefrontal cortex (PFC). Rats were sleep deprived by modified multi-platform method for 3 weeks. Totally 59 transcripts showed differential expressions in CSD group in contrast to controls; they included transcripts coding for caffeine metabolism, circadian rhythm, drug metabolism and some amino acid metabolism pathway. Among the 59 transcripts, 39 increased their expression and 20 decreased. Two transcripts can be specifically reversed with SKF38393, one of them is Homer1, which is related to 20 functional classifications and coding for Glutamatergic synapse pathway. Our findings in the present study indicate that long-term sleep deprivation may trigger the changes of some certain functions and pathways in the PFC, and lead to the dysfunction of this advanced neuron, and the activation of D1 receptor by SKF38393 might ameliorate these changes via modulation of some transcripts such as Homer1, which is involved in the Ca(2+) pathway and MAPK pathway related to Glutamatergic synapse pathway.