Genomics of hybrid parallel origin in Aquilegia ecalcarata.

BACKGROUND: The parallel evolution of similar traits or species provides strong evidence for the role of natural selection in evolution. Traits or species that evolved repeatedly can be driven by separate de novo mutations or interspecific gene flow. Although parallel evolution has been reported in many studies, documented cases of parallel evolution caused by gene flow are scarce by comparison. Aquilegia ecalcarata and A. kansuensis belong to the genus of Aquilegia, and are the closest related sister species. Mutiple origins of A. ecalcarata have been reported in previous studies, but whether they have been driven by separate de novo mutations or gene flow remains unclear. RESULTS: In this study, We conducted genomic analysis from 158 individuals of two repeatedly evolving pairs of A. ecalcarata and A. kansuensis. All samples were divided into two distinct clades with obvious geographical distribution based on phylogeny and population structure. Demographic modeling revealed that the origin of the A. ecalcarata in the Eastern of China was caused by gene flow, and the Eastern A. ecalcarata occurred following introgression from Western A. ecalcarata population. Analysis of Treemix and D-statistic also revealed that a strong signal of gene flow was detected from Western A. ecalcarata to Eastern A. ecalcarata. Genetic divergence and selective sweep analyses inferred parallel regions of genomic divergence and identified many candidate genes associated with ecologically adaptive divergence between species pair. Comparative analysis of parallel diverged regions and gene introgression confirms that gene flow contributed to the parallel evolution of A. ecalcarata. CONCLUSIONS: Our results further confirmed the multiple origins of A. ecalcarata and highlighted the roles of gene flow. These findings provide new evidence for parallel origin after hybridization as well as insights into the ecological adaptation mechanisms underlying the parallel origins of species.

[Malignant Adenomyoepithelioma of the Breast:Report of One Case and Literature Review].

Malignant adenomyoepithelioma(MAME)of the breast is a rare tumor with an incidence less than 1% of primary breast cancer.The low incidence and diverse histomorphology pose challenges to the accurate diagnosis and clinical management of MAME.This paper reports a case of MAME of the breast with an intraductal papillary growth pattern and summarizes the clinical features,pathological features,diagnosis,treatment,and prognosis of MAME of the breast in the last 5 years.

Laparoscopic D2+ lymph node dissection in patients with obesity and gastric cancer: A retrospective study.

D2 lymph node dissection is widely used in laparoscopic radical gastrectomy for gastric cancer, and its efficacy and safety are known for patients with obesity. Currently, D2+ lymph node dissection is also applied to certain patients with gastric cancer of later stages. Due to the high difficulty of D2+ surgery, it is more challenging to perform on patients with obesity. There is currently limited research on the efficacy and safety of D2+ surgery in obese patients with gastric cancer. The present study aimed to retrospectively analyze the clinical data of patients undergoing laparoscopic radical gastrectomy for gastric cancer admitted to a single gastroenterology department. Patients with a body mass index ≥25 kg/m2 were included in the study. A total of 149 patients were selected as the research subjects and divided into two groups. The observation group comprised 74 patients who underwent D2+ lymph node dissection, while the control group comprised 75 patients who underwent standard D2 lymph node dissection. The surgical performance, postoperative recovery and postoperative complications of the two groups were compared. The results showed that the rates of conversion to open surgery in the D2+ and D2 groups were 5.4% (4/74) and 2.7% (2/75), respectively, and were not significantly different. The duration of surgery in the D2+ group (282.55±23.02 min) was significantly longer than that in the D2 group (271.45±20.05 min). The mean number of lymph node dissections in the D2+ group was 28.57±7.19, which was significantly higher than that in the D2 group (25.29±6.41). No statistically significant differences in intraoperative blood loss, time to first flatus, postoperative hospitalization days, total hospitalization expenses or postoperative complications was detected between the two groups. There were no deaths in either group within the 30-day perioperative period. In addition, there was no significant difference in the 3-year overall survival rate between the two groups, while the 5-year overall survival rate of the D2+ group was significantly higher than that of the D2 group. For obese patients with gastric cancer, D2+ surgery may increase the duration of surgery and slightly increase intraoperative blood loss compared with standard D2 radical surgery, but does not increase the incidence of postoperative complications. Moreover, D2+ surgery increases the number of lymph node dissections and improves the 5-year survival rate of patients. Therefore, it may be concluded that laparoscopic D2+ lymph node dissection is safe and feasible for obese patients with gastric cancer.

The function role of HIGD1A in nonalcoholic steatohepatitis from chronic hepatitis B.

BACKGROUND: Accompanied by the growing prevalence of nonalcoholic fatty liver disease (NAFLD), the coexistence of chronic hepatitis B (CHB) and NAFLD has increased. In the context of CHB, there is limited understanding of the factors that influence the development of NASH. METHODS: We enrolled CHB combined NAFLD patients who had liver biopsy and divided them to NASH vs. non-NASH groups. A whole transcriptome chip was used to examine the expression profiles of long noncoding RNAs (lncRNAs) and mRNA in biopsied liver tissues. The function analysis of HIGD1A were performed. We knocked down or overexpressed HIGD1A in HepG2.2.15 cells by transient transfection of siRNA-HIGD1A or pcDNA-HIGD1A. In vivo investigations were conducted using hepatitis B virus (HBV) transgenic mice. RESULTS: In 65 patients with CHB and NAFLD, 28 were patients with NASH, and 37 were those without NASH. After screening 582 differentially expressed mRNAs, GO analysis revealed differentially expressed mRNAs acting on nicotinamide adenine dinucleotide phosphate (NADPH), which influenced redox enzyme activity. KEGG analysis also shown that they were involved in the NAFLD signaling pathway. The function analysis revealed that HIGD1A was associated with the mitochondrion. Then, both in vivo and in vitro CHB model, HIGD1A was significantly higher in the NASH group than in the non-NASH group. HIGD1A knockdown impaired mitochondrial transmembrane potential and induced cell apoptosis in HepG2.2.15 cells added oleic acid and palmitate. On the contrary, hepatic HIGD1A overexpression ameliorated free fatty acids-induced apoptosis and oxidative stress. Furthermore, HIGD1A reduced reactive oxygen species (ROS) level by increasing glutathione (GSH) expression, but Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Acetyl-CoA carboxylase (ACC) pathway was not involved. CONCLUSION: Both in vivo and in vitro CHB model, an upward trend of HIGD1A was observed in the NASH-related inflammatory response. HIGDIA played a protective role in cells against oxidative stress. Our data suggested that HIGD1A may be a positive regulator of NASH within the CHB context.

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.

The investigation of the ultrafast excited state deactivation mechanisms for coumarin 307 in different solvents.

The intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) processes of coumarin 307 (C307) in different solvents were investigated by performing steady-state/time-resolved transient absorption spectroscopic and steady-state photoluminescence spectroscopic characterizations in combination with time-dependent density functional theoretical calculation (TDDFT). The study unveiled the remarkable influence of solvent polarity and the strength of intermolecular hydrogen bonds formed between the solutes and solvents on the relaxation dynamics of the electronic excited state. Significantly, the emergence of the TICT state was observed in polar solvents, specifically dimethylformamide (DMF) and dimethyl sulfoxidemethanol (DMSO), owing to their inherent polarity as well as the enhanced intermolecular hydrogen bonding interactions. Interestingly, even in a weak polar solvent such as methanol (MeOH), the TICT state was also observed due to the intensified hydrogen bonding effects. Conversely, nonpolar solvents, exemplified by 1,4-dioxane (Diox), resulted in the stabilization of the ICT state due to the augmented N-H⋯O hydrogen bonding interactions. The experimental findings were corroborated by the computational calculations, thus ensuring the reliability of the conclusions drawn. Furthermore, schematic diagrams were presented to illustrate the mechanisms underlying the excited-state deactivation. Overall, this investigation contributes valuable mechanistic insights and provides a comprehensive understanding of the photochemical and photophysical properties exhibited by coumarin dyes.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.

Unraveling the effect of solvents on the excited state dynamics of C540A by experimental and theoretical study.

In this work, the excited-state dynamics including intramolecular charge transfer (ICT) and the redshift of C540A have been investigated in a series of solvents on the basis of the Kamlet-Taft solvatochromic parameters (π*, α, ß) using femtosecond transient absorption spectra and systematic theoretical calculation. We demonstrate that the redshift of the emission peak has a linear relationship with the α and π* scales and the effect of the π* scale is slightly stronger than that of the α scale. Meanwhile, the ICT rates can be suggested as relevant to not only the α scale but also the π* scale. Additionally, C540A-AN has proved that the excited state molecules have a unique inactivation mechanism because of the dark feature of the S1 (CT) state. The valuable mechanistic information gleaned from the excited-state dynamics by the experimental and theoretical study would facilitate the design of organic materials for prospective applications in photochemistry and photobiology.

The Diagnostic Values of Peptidoglycan, Lipopolysaccharide, and (1,3)-Beta-D-Glucan in Patients with Suspected Bloodstream Infection: A Single Center, Prospective Study.

This study aimed to assess the diagnostic values of peptidoglycan (PGN), lipopolysaccharide (LPS) and (1,3)-Beta-D-Glucan (BDG) in patients with suspected bloodstream infection. We collected 493 heparin anticoagulant samples from patients undergoing blood culture in Peking Union Medical College Hospital from November 2020 to March 2021. The PGN, LPS, and BDG in the plasma were detected using an automatic enzyme labeling analyzer, GLP-F300. The diagnostic efficacy for PGN, LPS, and BDG were assessed by calculating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). This study validated that not only common bacteria and fungi, but also some rare bacteria and fungi, could be detected by testing the PGN, LPS, and BDG, in the plasma. The sensitivity, specificity, and total coincidence rate were 83.3%, 95.6%, and 94.5% for PGN; 77.9%, 95.1%, and 92.1% for LPS; and 83.8%, 96.9%, and 95.9% for BDG, respectively, which were consistent with the clinical diagnosis. The positive rates for PGN, LPS, and BDG and the multi-marker detection approach for PGN, LPS, and BDG individually were 11.16%, 17.65%, and 9.13%, and 32.86% significantly higher than that of the blood culture (p < 0.05). The AUC values for PGN, LPS, and BDG were 0.881 (0.814−0.948), 0.871 (0.816−0.925), and 0.897 (0.825−0.969), separately, which were higher than that of C-reactive protein (0.594 [0.530−0.659]) and procalcitonin (0.648 [0.587−0.708]). Plasma PGN, LPS, and BDG performs well in the early diagnosis of bloodstream infections caused by Gram-positive and Gram-negative bacterial and fungal pathogens.

Alkalinity regulation in a sulfur autotrophic denitrifying filter substantially reduced total dissolved solids and sulfate in effluent.

Sulfur autotrophic denitrification (SAD) filters are considered a promising technology due to their stable and excellent performance in nitrogen removal, affordable costs, and operational advantages. In this work, a novel operational strategy that employed sodium bicarbonate as an alkalinity source in the autotrophic denitrification filter (S-SAD) was established. With the sufficient supply of alkalinity, the S-SAD reached an excellent denitrification performance (98.01%±0.43%) with a nitrate concentration of 10 mg/L in influent and hydraulic retention time of 3 hrs. The total dissolved solids increment and sulfate concentration in effluent were significantly reduced by one-third, compared with that of the traditional SAD process under the same conditions. The analysis of microbial community indicated that Thiobacilhus, typical species with the functions of simultaneous sulfur oxidation and denitrification, was evidently enriched in the S-SAD. Thus, this present work demonstrated a feasible, relatively cost-effective and environmentally friendly approach to operate SAD towards further application.

The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.

Increased interleukin-26 expression in proliferative diabetic retinopathy.

AIM: To detect the possible role of interleukin (IL)-26 in diabetic retinopathy (DR) patients. METHODS: Subjects were divided into diabetes without retinopathy (DWR) group (n=20), non-proliferative diabetic retinopathy (NPDR) group (n=20), proliferative diabetic retinopathy (PDR) group (n=20) and normal control group (n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA change of IL-26 in peripheral blood mononuclear cells (PBMCs) was assessed by real-time polymerase chain reaction. RESULTS: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients (without anti-VEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the mRNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the PBMCs. CONCLUSION: Protein and mRNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.

Hydrogen Sulfide Attenuates High Glucose-Induced Human Retinal Pigment Epithelial Cell Inflammation by Inhibiting ROS Formation and NLRP3 Inflammasome Activation.

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various high glucose-induced insult models. However, it remains unknown whether H2S protects human retinal pigment epithelial cells (RPE cells) from high glucose-induced damage. In the current study, cell viability, proinflammatory cytokines, ROS, and inflammasome markers were compared in a low glucose- and high glucose-induced cell culture system. The antioxidant N-acetylcysteine (NAC), NLRP3 siRNA, and NaHS were used to test RPE cell responses. The results demonstrate that compared with the low-glucose culture, high glucose triggered higher cell death and increased IL-18 and IL-1ß mRNA expression and protein production. Furthermore, high glucose increased the mRNA expression levels of NLRP3, ACS, and caspase-1. Notably, NAC, a ROS scavenger, could attenuate high glucose-induced ROS formation and IL-18 and IL-1ß mRNA and protein expression and block inflammasome activation. Silencing the NLRP3 gene expression also abolished IL-18 and IL-1ß mRNA and protein expression. Intrudingly, H2S could ameliorate high glucose-induced ROS formation, IL-18 and IL-1ß expression, and inflammasome activation. Taken together, the findings of the present study have demonstrated that H2S protects cultured RPE cells from high glucose-induced damage through inhibiting ROS formation and NLRP3 inflammasome activation. It might suggest that H2S represents a potential therapeutic target for the treatment of diabetic retinopathy.

The Synthesis of ³H-Labelled 8-Azido-N6-Benzyladenine and Related Compounds for Photoaffinity Labelling of Cytokinin-Binding Proteins.

The biology of the group of plant hormones termed cytokinins is reviewed to reveal areas where further studies of cytokinin-binding proteins could be significant. Such areas include: inhibition of human tumour cell growth by cytokinin ribosides, the role of cytokinins in the development of diverse micro-organisms including the cyanobacteria and Mycobacterium tuberculosis, the very rapid responses of plant cells to exogenous cytokinins, and other aspects of cytokinin plant biology. Photoaffinity labelling (PAL) coupled to the recent advances in HPLC of proteins and mass spectral analysis and sequencing of proteins, may have relevance to these areas. To facilitate PAL, we present experimental details for two methods for synthesis of 8-azido-N6-benzyladenine, which has the azido affinity group in the preferred position of the purine ring. Synthesis from [2-³H]adenosine yielded the above-mentioned PAL reagent with ³H in the purine ring and also gave labelled 9-riboside and 8-azido-N6,9-dibenzyladenine. 8-Azido-N6-benzyladenine was also prepared from 6,8-dichloropurine by a facile synthesis, which would allow a label to be sited in the benzyl group where substituents can also be introduced to vary cytokinin activity. The use of inactive cytokinin analogues in assessing the significance of PAL is discussed.

The Feasibility of Hand-assisted Laparoscopic and Laparoscopic Multivisceral Resection Compared With Open Surgery for Locally Advanced Colorectal Cancer.

BACKGROUND: The role of hand-assisted laparoscopic and pure laparoscopic surgery for locally advanced colorectal cancer invading or adhering to neighboring organs is controversial. This study evaluated the safety and feasibility of laparoscopic multivisceral resection for colorectal cancer. PATIENTS AND METHODS: This study included 201 patients who underwent multivisceral resection for locally advanced colorectal cancer from January 2007 to December 2013 in the Department of General Surgery, Henan Provincial Hospital. Perioperative outcomes and long-time outcomes were compared among hand-assisted laparoscopic, laparoscopic and open resections. RESULTS: Estimated blood loss, wound length, time to the first flatus, and postoperative hospital stay were significantly less or shorter in the hand-assisted laparoscopic surgery (HALS) and laparoscopic surgery group than in open surgery (OS) group. There were no significant differences in tumor size, retrieved lymph nodes, and R0 resection rate of the primary tumor among the 3 groups. Surgeries started as laparoscopic surgery were completed in that manner 76.6% of the time with 10.6% being converted to OS and 12.8% converted to HALS and there were only 2 conversions (2.2%) to OS in the HALS group. No significant difference was noted for overall morbidity rate and reoperation rate among the 3 groups. The overall observed 5-year survival rate was 60.5% in the laparoscopic group, 55.4% in the HALS group, and 47.7% in the open group. There was no significant difference among the 3 groups in the 5-year survival rate. CONCLUSIONS: Hand-assisted laparoscopic and pure laparoscopic multivisceral resection for locally advanced colorectal cancer is safe and feasible in selected patients. HALS can be used judiciously to reduce the rate of conversion to an open procedure and may be a better alternative for laparoscopic approach.

Open Versus Hand-assisted Laparoscopic Total Gastric Resection With D2 Lymph Node Dissection for Adenocarcinoma: A Case-Control Study.

OBJECTIVE: A case-control study was conducted to investigate the feasibility and safety of hand-assisted laparoscopic total gastrectomy (HALTG) with D2 lymphadenectomy for gastric cancer as opposed to traditional open total gastrectomy (OTG). METHODS: One hundred fifty-four patients suffering cardia, upper, middle, or whole gastric cancer operated in our department from February 2009 to February 2012 were divided into 2 groups: the open total gastrectomy group (the OTG group) and the hand-assisted laparoscopic total gastrectomy group (the HALTG group). Operative time, estimated blood loss, number of lymph node retrieval, time to the first flatus, and postoperative hospital stay were compared between the 2 groups. RESULTS: HALTG was associated with significantly less operative blood loss, shorter time to the first flatus and shorter postoperative hospital stay, but longer operative time, compared with OTG. There were no significant differences in tumor size, retrieved lymph nodes, American Joint Committee on Cancer/Union International Control Cancer staging and tumor location between the 2 groups. Negative resection margins were obtained in all patients who had undergone a hand-assisted laparoscopic gastrectomy (100%) and in all but 2 patients in the open group (97.6%). The overall observed 5-year survival rate was 56.5% in the HALTG group and 51.8% in the OTG group (P=0.0001, log-rank test). CONCLUSIONS: HALTG is a safe, feasible, and oncologically sound procedure and has advantages over ODG.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model.

AIM: To examine the expression of high mobility group box-1 (HMGB-1) and intercellular adhesion molecule-1 (ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB) and blood-brain barrier (BBB) in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM) model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P<0.01). The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA), total cholesterol (TC), total triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the DM rats significantly higher than those in the controls (all P<0.01). HMGB-1 (0.96±0.03, P<0.01) and ICAM-1 (0.76±0.12, P<0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P<0.01) and ICAM-1 (1.15±0.08, P<0.01) levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P<0.01). However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.

Myricetin suppresses p21-activated kinase 1 in human breast cancer MCF-7 cells through downstream signaling of the ß-catenin pathway.

As a main active compound in the bark of waxberry (Myrica rubra), myricetin is a macrocyclic diarylheptanoid, and can trigger the apoptosis of HeLa and PC3 cells. The aim of the present study was to elucidate the anticancer effect of myricetin on human breast cancer MCF-7 cells and to explore the possible mechanisms of action. MCF-7 cells were treated with different concentrations of myricetin (0-80 µM) for 12, 24 and 48 h. In the present study, we found that myricetin suppressed the cell viability of the MCF-7 cells at least partly through the induction of apoptosis as determined by MTT assay and flow cytometry. Western blot analysis revealed that myricetin effectively suppressed the protein expression of p21-activated kinase 1 (PAK1), MEK and phosphorylated extracellular mitogen-activated protein kinase (ERK1/2). In addition, treatment of myricetin activated glycogen synthase kinase-3ß (GSK3ß) and Bax protein expression, and inhibited ß-catenin/cyclin D1/proliferating cell nuclear antigen (PCNA)/survivin and promoted caspase-3 activity in the MCF-7 cells. These results demonstrated that myricetin suppressed the cell viability of human breast cancer MCF-7 cells through PAK1/MEK/ERK/GSK3ß/ß-catenin/cyclin D1/PCNA/survivin/Bax-caspase-3 signaling.

Hand-assisted laparoscopic total gastrectomy with regional lymph node dissection for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic-assisted distal gastrectomy has been applied to the treatment of gastric cancer. However, there have been few reports on the laparoscopic-assisted total gastrectomy for advanced gastric cancer, mainly because of the difficulty of the procedure. METHODS: Here, we report a series of cases where the hand-assisted laparoscopic total gastrectomies with regional lymph node dissection were performed successfully. RESULTS: The average operative time was 245 minutes. The mean blood loss was 110 mL. The number of dissected lymph nodes per patient was beyond 15 nodes satisfying a reliable evaluation of nodal status. All resection specimens had no residual tumor at the proximal or distal resection margins. The mean oral feeding was 3.6 days. The mean postoperative length of stay was 8.7 days. CONCLUSIONS: The hand-assisted laparoscopic D2 total gastrectomy for advanced gastric cancer is both technically feasible and safe.