scHybridBERT: integrating gene regulation and cell graph for spatiotemporal dynamics in single-cell clustering.

Graph learning models have received increasing attention in the computational analysis of single-cell RNA sequencing (scRNA-seq) data. Compared with conventional deep neural networks, graph neural networks and language models have exhibited superior performance by extracting graph-structured data from raw gene count matrices. Established deep neural network-based clustering approaches generally focus on temporal expression patterns while ignoring inherent interactions at gene-level as well as cell-level, which could be regarded as spatial dynamics in single-cell data. Both gene-gene and cell-cell interactions are able to boost the performance of cell type detection, under the framework of multi-view modeling. In this study, spatiotemporal embedding and cell graphs are extracted to capture spatial dynamics at the molecular level. In order to enhance the accuracy of cell type detection, this study proposes the scHybridBERT architecture to conduct multi-view modeling of scRNA-seq data using extracted spatiotemporal patterns. In this scHybridBERT method, graph learning models are employed to deal with cell graphs and the Performer model employs spatiotemporal embeddings. Experimental outcomes about benchmark scRNA-seq datasets indicate that the proposed scHybridBERT method is able to enhance the accuracy of single-cell clustering tasks by integrating spatiotemporal embeddings and cell graphs.

Successful treatment of advanced muscle-invasive bladder cancer with the combined therapy of toripalimab and chemotherapy: a case report.

Bladder cancer is the most common malignancy in the urinary system, and muscle-invasive bladder cancer (MIBC) accounts for 25-30% among all types of bladder cancers. Although MIBC can be treated by surgery and chemotherapy, favorable outcomes can still not be obtained. In recent years, the emergence of immunotherapy represented by programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors and other immune checkpoint inhibitors provides attractive prospects for the treatment of advanced bladder cancer. PD-1/PD-L1 inhibitors can block the binding of PD-1/PD-L1, which can block negative immunomodulatory signals, thereby improving anti-tumor immune activity. In this article, we reported a case of advanced MIBC who achieved complete pathological remission after receiving the combined therapy of toripalimab and chemotherapy, which could provide clinical data for the treatment of bladder cancer with triprizumab.

Determination of components in Radix paeoniae rubra based on QAMS.

The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.

Protective roles of liraglutide against brain injury of streptozotocin induced diabetic rats.

Our study aimed to explore the impacts of liraglutide on brain dysfunction of type 2 diabetes mellitus. Rats in liraglutide treatment group were diabetic rats further received daily intraperitoneal administration of liraglutide for continuous 6 weeks. Body weight and blood glucose were measured weekly. Vascular structure changes in brain tissues were evaluated by Periodic acid-Schiff (PAS) staining. Angiopoietin-2 (ANG-2), high-mobility group box 1 (HMGB-1), CD105, NeuN, Oligo-2 in brain tissues were measured by immunohistochemistry staining and ANG-2, HMGB-1, and matrix metalloproteinase-9 (MMP-9) were detected by western blotting. Blood glucose levels of rats in diabetic model group were significantly elevated and blood glucose levels of rats in liraglutide treatment group were reduced to comparable levels with control group. PAS staining showed vascular basement membrane of rats in the diabetic model group was thicker than that of the control group. ANG-2, HMGB1 and MMP-9 were up-regulated in the diabetic model group comparing the control group, while down-regulated after treated with liraglutide (p<0.05). NeuN expressions were significantly higher in liraglutide treatment group. Liraglutide may have protective roles against brain injury of streptozotocin induced diabetic rats by inhibiting HMGB1, which further suppressing the MMP-9 and ANG-2.

The Microenvironment of Tongue Cancer.

Cancer cells interact with and remodel the surrounding microenvironment. An increasing number of studies focus on tongue tumor microenvironment (TME) to find novel approaches to investigate tongue cancer, indicating that tongue tumor microenvironment is recognized as a critical element for tongue tumor development and metastasis and as a potential therapeutic target. In this paper, we review the extrinsic features of the tongue tumor microenvironment, including its various components, and the intrinsic characteristics of TME, including heterogeneity, cell death, and metastatic potential. We also report on the cross talk between these intrinsic and extrinsic components. We believe that the exploration of the tongue tumor microenvironment can provide guidance for the treatments and improve the overall survival and quality of patients' lives.

[Effect of Panax japonicus saponin â £a on alleviating nonalcoholic steatohepatitis by regulating miR-17-5p/MFN2 signaling pathway].

To study the effect of Panax japonicas saponin Ⅳa(SPJ-Ⅳa) on nonalcoholic steatohepatitis(NASH) through miR-17-5 p/MFN2 signaling pathway. The nonalcoholic steatohepatitis model was induced by a high-fat diet combined with CCl_4 in Balb/c male mice. The mouse serum and liver were collected, the body weight and liver weight were measured, the liver index was calculated, and the serum biochemical indicators alanine amino transferase(ALT), triglyceride(TG), and glucose(Glu) were measured. The morphological changes in the liver were detected by HE and Masson staining, Real-time PCR was used to detect lipid metabolism-related genes, inflammation-related genes interleukin-6(IL-6) and interleukin-1ß(IL-1ß), miR-17-5 p and MFN2 expressions, and Western blot was used to detect MFN2 protein expression level. Compared with the normal control group, the liver index in the HFD+CCl_4 group was significantly increased, and the contents of ALT, TG, and Glu were significantly increased; the morphology showed obvious steatosis and collagen fiber deposition; mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p increased significantly, the mRNA expression level of MFN2 decreased significantly, and the protein level of MFN2 decreased. After intervention with SPJ-Ⅳa, the levels of ALT, TG and Glu decreased, morphological steatosis decreased, collagen fiber deposition decreased, and mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p decreased. The mRNA expression level of MFN2 increased, and the protein level of MFN2 also increased. The results of this study indicated that miR-17-5 p/MFN2 signaling pathway may be involved in the occurrence and development of NASH, and SPJ-Ⅳa had a protective effect on NASH, its mechanism may be related to the regulation of miR-17-5 p/MFN2 signaling pathway.

Optimized preparation of Phragmites australis activated carbon using the Box-Behnken method and desirability function to remove hydroquinone.

In this study, preparation of Phragmites australis activated carbon (PAAC) was optimized and applied for the removal of hydroquinone from aqueous solution. The Box-Behnken surface design (33) was used to statistically visualize the interactions among microwave power (A), microwave radiation time (B) and the ingredient ratio (C) (H3PO4: P. australis powder, in g). The desirability function was utilized to simultaneously optimize the multi-response indicators. A regression analysis showed that the experimental data of BBD optimization experimental results fit well to a quadratic model. PAAC was characterized according to its morphology, structure and composition. Dynamic adsorption data showed that the best fit was obtained by a pseudo-second-order model and the Freundlich isotherm model. The maximum adsorption capacity for hydroquinone adsorption onto PAAC was 156.25 mg/g at 30 ℃ and the adsorption mechanism may be attributed to multi-layer surface and chemisorption via donor-acceptor and coupling interaction of the electron. The present study showed that PAAC has the potential for use as a biosorbent for the adsorption treatment of water pollutants.

In Vitro Effects of HAS-2 Gene Silencing on the Proliferation and Apoptosis of the MCF-7 Human Breast Cancer Cell Line.

BACKGROUND: Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. This study is aimed to investigate the effects of silencing the HAS-2 gene on the proliferation and apoptosis of human breast cancer cells. METHODS: MCF-7 cells were collected and assigned into control, scrambled siRNA and HAS-2- siRNA groups. After transfection, the morphological changes in the MCF-7 cells were observed using phase contrast microscopy. qRT-PCR and Western blot assays were used to detect the mRNA and protein expression of apoptosis-related proteins. CCK-8 and flow cytometry were performed to evaluate cell proliferation, the cell cycle and apoptosis. RESULTS: In the control and the scrambled siRNA groups, cells grew adhered to the wall and mainly showed a spindle shape with a clear nucleolus. Compared with the control and scrambled siRNA groups, increases in the number of cells in early apoptosis and metaphase cells in apoptosis were observed in the HAS-2-siRNA group. The HAS-2-siRNA group showed decreased expression of HAS-2 relative to that in the control and scrambled siRNA groups. No significant differences in cell proliferation, cell cycle distribution or apoptosis were noted between the control and scrambled siRNA groups. In the HAS-2-siRNA group, the cell proliferation ability decreased significantly, but the number of cells in the G0/G1 stage, the number of apoptotic cells and the expression of caspase-3 and caspase-9 increased significantly. CONCLUSION: Our findings indicate that HAS-2 gene silencing may inhibit proliferation and promote apoptosis in the MCF-7 human breast cancer cell line.

A Novel Method for Detection the Deafness-Associated Mitochondrial A1555G and C1494T Mutations.

BACKGROUND: To develop a novel method for molecular detection of deafness-associated mitochondrial A1555G and C1494T mutations. METHODS: We designed four primers that specifically bind to human mitochondrial 12S rRNA. PCR amplification of DNA samples including the A1555G, C1494T, and healthy controls is performed. The products are analyzed by the electrophoresis. RESULTS: We found that the PCR products of DNA samples with A1555G mutation consisted of two specific bands: 226 bp and 736 bp. While amplification of DNA samples with the C1494T mutation resulted in two fragments: 488 bp and 736 bp. CONCLUSIONS: Our study establishes a convenient, accurate, and cost-effective method for molecular diagnosis of deafness-associated mitochondrial A1555G and C1494T mutations.

The role of retinoic acid receptors in the signal pathway of all-trans retinoic acid-induced differentiation in adriamycin-induced podocyte injury.

All-trans retinoic acid (ATRA) plays an essential role in cell survival and differentiation by binding to retinoic acid receptors (RARs), including RAR-α, RAR-ß, and RAR-γ. Injury to podocytes is the most frequent cause of glomerulosclerosis (GS). This study was performed to investigate which of the RAR subtypes is involved in the signal pathway of ATRA-induced differentiation of injured podocytes. ATRA (0.1 µM) was administered to Adriamycin (ADR)-induced, injured podocytes, in vitro. Morphological changes were observed. The protein/mRNA expression of podocin, nephrin, transforming growth factor ß1(TGF-ß1), and the RARs (RAR-α,ß,γ) was measured by RT-PCR and Western blotting. ATRA treatment ameliorated cell hypertrophy and reduced the shedding of the cytoplasm which was observed under light microscope and the extension of the foot processes was observed under scan electron microscope. Compared with the injured podocytes, ATRA exposure significantly increased the protein/mRNA expression of nephrin and podocin and it markedly reduced TGF-ß1 (all p < 0.05). Compared with the injured podocytes, the protein/mRNA expression of RAR-α and RAR-γ was significantly increased after ATRA exposure; however, the expression level of RAR-ß was not significantly different. The RAR-α/γ protein expression level was positively correlated with nephrin and podocin (-α, r = 0.637, 0.663; -γ, r = 0.882, 0.878; all p < 0.05), and negatively correlated with TGF-ß1 (-α, r = -0.650; -γ, r = -0.739; all p < 0.05). The RAR-ß protein expression level was not correlated with nephrin, podocin and TGF-ß1 (r = -0.312, 0.079, -0.279; all p > 0.05). In conclusion, RAR-α/γ (and RAR-ß to a lesser degree) may be involved in the signal pathway of ATRA-induced differentiation in injured podocytes.

S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis.

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

Meta-analysis of randomized controlled trials on the efficacy of probiotics in Helicobacter pylori eradication therapy in children.

UNLABELLED: The efficacy of probiotics supplementation in children undergoing Helicobacter pylori (H. pylori) eradication therapy remains controversial. This study aimed to meta-analyze whether probiotics supplementation in triple therapy could improve H. pylori eradication rates and reduce therapy-related side effects in children. Electronic databases PubMed and Embase were searched to identify all randomized controlled trials in pediatric patients comparing probiotics supplementation with placebo or no extra intervention in H. pylori eradication therapy. Two authors independently extracted the data. Results were expressed as odds ratios (ORs) and accompanying 95 % confidence intervals (CIs). Stata version 12.0 was used to perform all statistical analyses. Seven studies consisting of 508 pediatric patients were included in our study. The pooled ORs (studies n = 7) of eradication rates by intention-to-treat and per-protocol analysis in the probiotics group versus the control group were 1.96 (95 % CI 1.28-3.02) and 2.25 (95 % CI 1.41-3.57), respectively. The pooled OR (studies n = 5) of incidence of total side effects was 0.32 (95 % CI 0.13-0.79), with significant heterogeneity observed (I (2) = 71.9 %). CONCLUSION: Probiotics supplementation in triple therapy for H. pylori infection may have beneficial effects on eradication and therapy-related side effects, particularly diarrhea, in children.

Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a meta-analysis.

PURPOSE: An association between the INS VNTR polymorphisms and polycystic ovary syndrome (PCOS) susceptibility has been reported in previous studies, but the results were inconsistent. This study was conducted to explore this association using meta-analysis. METHODS: PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched according to predefined criteria for all relevant studies published up to August 2013. Four genetic models, together with odds ratios (ORs) and 95 % confidence intervals (CI), were calculated. Subgroup analyses were performed by ethnicity, anovulatory PCOS, and Hardy-Weinberg equilibrium (HWE) in the controls. RESULTS: In total, 13 case-control studies, including 1,767 cases and 4,108 controls, were included. No significant association was detected in overall population in all models (III/III vs. I/I: OR = 1.200, 95%CI = 0.866-1.664, P=0.277; I/III vs. I/I: OR = 1.041, 95%CI = 0.880-1.232, P=0.637; III/III + I/III vs. I/I: OR = 1.191, 95%CI = 0.912-1.554, P=0.199; III/III vs. I/III + I/I: OR = 1.100, 95%CI = 0.816-1.484, P=0.531), the same as in Caucasian and Asian populations. When the studies were limited to conform to HWE, the results remained persistent and robust. The anovulation subgroup showed significantly elevated risk in the I/III vs. I/I (OR = 1.460, 95%CI = 1.017-2.095, P=0.040). CONCLUSIONS: This meta-analysis revealed no significant association between INS VNTR polymorphisms and the risk of PCOS in the overall population, while it supported that variance may be associated with susceptibility to PCOS with anovulation. Further confirmation is needed from more well-designed and larger studies.

Hyperacusis questionnaire and event-related potential correlation in migraine patients.

This study aims to investigate auditory hypersensitivity and cortical function in migraine patients using the Hyperacusis Questionnaire and the Event-Related Potential (ERP) technique. The study analyzes alterations in the latency and amplitude of the event-related potentials MMN and P300 components. The findings contribute to a better understanding of the physiological relationship between migraine and auditory hypersensitivity. Seventeen migraine patients were admitted to the outpatient clinic of the Department of Otorhinolaryngology-Head and Neck Surgery at Peking University People's Hospital from June 2023 to September 2023. Nineteen matched healthy subjects were also selected. All participants underwent the pure tone audiometry and the auditory brainstem response test to determine hearing thresholds, the Hyperacusis Questionnaire, the Tinnitus Handicap Inventory, and an ERP examination. The Oddball classical paradigm was used as the stimulation task, and electroencephalography signals were recorded synchronously. The scores of the Hyperacusis Questionnaire, latency and amplitude of MMN and P300 component were compared between the migraine group and the control group, and their correlation was analyzed. The latency of MMN at the Fz and Cz sites in migraine patients was significantly shorter than that in the control group (P < 0.05), and the amplitudes were significantly higher than those in the control group (P < 0.05). The variances in latency and amplitude of P300 at Cz and Pz sites in migraine patients were not statistically significant when compared with the control group. (P > 0.05). The Hyperacusis Questionnaire was negatively correlated with MMN latency, with a correlation coefficient of - 0.374 (P = 0.025), and positively correlated with MMN amplitude, with a correlation coefficient of 0.378 (P = 0.023). There was no significant similarity between the Hyperacusis Questionnaire and P300 latency and amplitude (P > 0.05). Overall, auditory hypersensitivity was enhanced in individuals with migraines compared to healthy individuals, leading to faster information processing, while there may be less impairment in cognitive function.

Periodontitis promotes the progression of diabetes mellitus by enhancing autophagy.

Objective: This study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic ß cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM). Methods: Sprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread. Alveolar bone resorption was assessed using Micro-CT, blood glucose levels were measured with a blood glucose meter, pancreatic tissue pathology was examined through HE staining, and the expression of autophagy-related proteins Beclin1 and LC3II/LC3I was analyzed using Western blotting. Results: Micro-CT results revealed more pronounced alveolar bone resorption and root bifurcation exposure in the PD and DP groups compared to the control group, with the DP group exhibiting the most severe condition. HE staining demonstrated the formation of periodontal pockets, severe alveolar bone destruction, and abnormal pancreatic islet tissue morphology in the PD and DP groups. The serum levels of IL-6, TNF-α, and IL-1ß increased sequentially in the control, DM, PD, and DP groups (P < 0.05). Relative expressions of GCK and GLUT-2 mRNA decreased in the PD group compared to the control group (P > 0.05), while the mRNA expressions in the DP and DM groups increased (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Western blot results indicated increased expression levels of autophagy proteins Beclin1 and LC3II/LC3I in the DM and DP groups compared to the control group (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Conclusion: The findings demonstrate that periodontal inflammatory factors may promote the enhancement of pancreatic cell autophagy in diabetic rats.

Predictors of stricture after endoscopic submucosal dissection of the esophagus and steroids application.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a reliable method to resect early esophageal cancer. Esophageal stricture is one of the major complications after ESD of the esophagus. Steroid prophylaxis for esophageal strictures, particularly local injection of triamcinolone acetonide (TA), is a relatively effective method to prevent esophageal strictures. However, even with steroid prophylaxis, stenosis still occurs in up to 45% of patients. Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients. AIM: To identify the predictors of esophageal strictures after steroids application. METHODS: Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion- and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study. The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis. RESULTS: A total of 120 patients were included in the analysis. In the oral prednisone and oral prednisone combined with local tretinoin injection groups, the stenosis rates were 44/53 (83.0%) and 56/67 (83.6%), respectively. Among them, univariate analysis showed that the lesion circumference (P = 0.01) and submucosal injection solution (P = 0.04) showed significant correlation with the risk of stenosis formation. Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports, such as additional chemoradiotherapy and tumor location. We identified a lesion circumference < 5/6 (OR = 0.19; P = 0.02) and submucosal injection of sodium hyaluronate (OR = 0.15; P = 0.03) as independent predictors of on esophageal stricture formation. CONCLUSION: Steroid prophylaxis effectively prevents stenosis. Moreover, the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures. Additional interventions should be considered in high-risk patients.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

OBJECTIVE: To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. METHODS: A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. RESULTS: In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). CONCLUSION: The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

Age-, season- and gender-specific reference intervals of serum 25-hydroxyvitamin D3 for healthy children (0 ~ 18 years old) in Nanning area of China.

Establishing specific reference intervals (RIs) of serum 25-hydroxyvitamin D3 [25(OH)D] for children is essential for improving the accuracy of diagnosis and prognosis monitoring of diseases such as rickets and growth retardation. The study including 6,627 healthy children was conducted to establish specific RIs of 25(OH)D for children in Nanning area of China. The results showed that there were statistically significant differences among age, season, and gender of serum 25(OH)D levels, and the age-specific RIs of serum 25(OH)D were 20.3 ~ 53.6 ng/mL for 0 ~ ≤ 1 year and 18.9 ~ 49.6 ng/mL for 2 ~ ≤ 3 years. The age-, season-specific RIs of serum 25(OH)D for 4 ~ ≤ 6 years in spring-summer and autumn-winter were 15.8 ~ 42.6 ng/mL and 15.2 ~ 37.7 ng/mL, respectively. The age-, gender-specific RIs of serum 25(OH)D for 7 ~ ≤ 18 years for males and females were 12.1 ~ 36.1 ng/mL and 10.8 ~ 35.3 ng/mL, respectively. This study successfully established the RIs of serum 25(OH)D, which may help to improve disease diagnosis and monitoring for children in the Nanning area of China.

Vascular endothelial growth factor regulates primate choroid-retinal endothelial cell proliferation and tube formation through PI3K/Akt and MEK/ERK dependent signaling.

Vascular endothelial growth factor (VEGF) is a hypoxia-induced angiogenic protein that exhibits a broad range of biological and pathological effects in wet age-related macular degeneration and proliferative diabetic retinopathy. However, its specific mechanism is still not fully understood. Here, we examined the effects of VEGF on choroid-retinal endothelial cells (RF/6A) proliferation and tube formation, and the underlying signal pathways responsible in this process. RF/6A cells were pretreated with MEK inhibitor or PI3K inhibitor, and then incubated in a hypoxia chamber. Real-time PCR and Western blot analysis were carried out to explore VEGF expression on mRNA and protein levels. Hypoxia inducible factor-1α (HIF-1α) and VEGFR2 expression levels were also investigated in the presence and absence of hypoxic conditions. CCK-8 analysis and tube formation assay were tested under hypoxia, exogenous recombinant VEGF, and different signal pathway inhibitors, respectively. Mean while, the PI3K/Akt and MEK/ERK pathways in this process were also investigated. Our results showed that VEGF, HIF-1α, VEGFR2, p-ERK, and p-Akt were up-regulated in RF/6A cells under hypoxic conditions. MEK inhibitor (PD98059) and PI3K inhibitor (LY294002) decreased ERK and Akt activity, respectively, and reduced VEGF expression. VEGF-induced RF/6A proliferation and tube formation requires MEK/ERK and PI3K/Akt signaling, and both of the two pathways were needed in regulating VEGF expression. These suggest that VEGF plays an important role in RF/6A proliferation and tube formation, and MEK/ERK and PI3K/Akt pathway may be responsible for this process.

XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms in esophageal cancer risk: a meta-analysis.

BACKGROUND: The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. AIM: To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis. METHODS: Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. RESULTS: According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053-1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093-1.624, P = 0.005). CONCLUSIONS: Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.