Clinicopathological features of esophageal schwannomas in mainland China: systematic review of the literature.

OBJECTIVE: Esophageal schwannoma (ES) are rare and mostly benign neurogenic tumors. The clinical misdiagnosis rate of it is high. In this study, the clinicopathologic features of ES in mainland China were studied to better understand the disease and improve the diagnosis and treatment rate. METHODS: A systematic review was conducted in accordance with PRISMA guidelines. The keywords "esophageal schwannoma", "esophageal neurinoma" and "esophageal neurilemoma" were searched for databases such as Pubmed, EMbase, Wanfang Database and Chinese National Knowledge Infrastructure. The search time frame for database was until July 2019. Combined with our patient, the clinicopathological data and the diagnosis and treatment of ES were summarized. RESULTS: ES occurs in the upper part of the mediastinum and in the thoracic esophagus in most patients in the neck, upper and middle segments. CT and PET/CT examinations can be used for diagnosis, but the differentiation value of both benign and malignant ES is similar. The histopathological findings of forceps biopsy specimens are often difficult to diagnose, and deep tissue biopsies may increase pathological accuracy. EUS-FNA is also recommended for ES diagnosis, but it may also be misdiagnosed. Pathological features include a fusiform arrangement in a palisade-like structure or a tumor cell arranged in a network to form a loose structure. ES characteristic immunohistochemistry results showed that S-100 protein has strong immunological activity. CONCLUSION: The definitive diagnosis requires immunohistochemistry, especially immunological reaction with S-100 protein. The appropriate treatment plan should be selected according to the diameter of the lesion. The overall prognosis of ES is good, but attention should be paid to follow-up.

Association between the LIPG polymorphisms and serum lipid levels in the Maonan and Han populations.

INTRODUCTION: The Maonan population is a relatively isolated minority in China. Little is known about endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. The present study aimed to detect the association of several LIPG SNPs and environmental factors with serum lipid levels in the Chinese Maonan and Han populations. METHODS: In total, 773 subjects of Maonan ethnicity and 710 participants of Han ethnicity were randomly selected from our previous stratified randomized samples. Genotypes of the LIPG rs2156552, rs4939883 and rs7241918 SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: The allelic (rs2156552, rs4939883 and rs7241918) and genotypic (rs2156552 and rs4939883) frequencies were different between the two ethnic groups (p < 0.05-0.01). The minor allele carriers had lower apolipoprotein (Apo)A1/ApoB ratio (rs2156552 and rs7241918), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)A1 (rs2156552) levels and higher ApoB levels (rs4939883) in the Han population, and lower HDL-C (rs2156552, rs4939883 and rs7241918) levels in the Maonan minority than the minor allele non-carriers (p < 0.0167 after Bonferroni correction). Subgroup analyses according to sex showed that the minor allele carriers had a lower ApoA1/ApoB ratio (rs2156552 and rs7241918) and higher ApoB levels (rs7241918) in Han males, and lower ApoA1 and HDL-C levels in Maonan females than the minor allele non-carriers (p < 0.0167-0.001). CONCLUSIONS: The present study demonstrates the association between the LIPG polymorphsims and serum lipid levels in the two ethnic groups. These associations might have an ethnic- and or/sex-specificity.

LIPG SNPs, their haplotypes and gene-environment interactions on serum lipid levels.

BACKGROUND: Maonan nationality is a relatively conservative and isolated minority in the Southwest of China. Little is known about the association of endothelial lipase gene (LIPG) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. METHODS: A total of 1280 subjects of Maonan nationality and 1218 participants of Han nationality were randomly selected from our previous stratified randomized samples. Genotypes of the four LIPG SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism, and then confirmed by direct sequencing. RESULTS: Several SNPs were associated with high-density lipoprotein cholesterol (rs3813082, rs2000813 and rs2097055) in the both ethnic groups; total cholesterol and apolipoprotein (Apo) A1 (rs2000813) in Han nationality; and low-density lipoprotein cholesterol, ApoB, triglyceride (rs2097055) and ApoA1 (rs3819166) in Maonan minority (P < 0.0125 for all after Bonferroni correction). The commonest haplotype was rs3813082T-rs2000813C-rs2097055T-rs3819166A (Han, 44.2% and Maonan, 48.7%). The frequencies of the T-C-T-A, T-C-T-G, T-T-C-G and G-T-C-G haplotypes were different between the Maonan and Han populations (P < 0.05-0.001). The associations between haplotypes and dyslipidemia were also different in the Han and/or Maonan populations (P < 0.05-0.001). CONCLUSIONS: The differences in serum lipid profiles between the two ethnic groups might partly be attributed to these LIPG SNPs, their haplotypes and gene-environmental interactions. TRIAL REGISTRATION: Retrospectively registered.

Association of the SPTLC3 rs364585 polymorphism and serum lipid profiles in two Chinese ethnic groups.

BACKGROUND: Little is known about the association of the single nucleotide polymorphism (SNP) of rs364585 near serine palmitoyl-transferase long-chain base subunit 3 gene (SPTLC3) and serum lipid profiles. The present study was detected the association of the SPTLC3 rs364585 SNP and several environmental factors with serum lipid profiles in the Han and Jing populations. METHODS: Genotyping of the SPTLC3 rs364585 SNP was performed in 824 unrelated individuals of Han and 783 participants of Jing by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: There was no significant difference in either genotypic or allelic frequencies between Han and Jing, or between males and females of the both ethnic groups. The levels of serum low-density lipoprotein cholesterol (LDL-C) and the ratio of apolipoprotein (Apo) A1 to ApoB in Han; and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C in Jing were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001). Subgroup analysis according to sex showed that the levels of LDL-C in Han males; TC and LDL-C in Jing males; and HDL-C and LDL-C in Jing females were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001), the A allele carriers had higher LDL-C and TC levels, and lower HDL-C levels than the A allele non-carriers. Serum lipid traits were also associated with several environmental factors in the Han and Jing populations, or in males and females of the both ethnic groups. CONCLUSIONS: The present study demonstrates the association between the SPTLC3 rs364585 SNP and serum TC, HDL-C and LDL-C levels in our study populations. These associations might have ethnic- and/or sex-specificity. TRIAL REGISTRATION: Retrospectively registered.

Anti-miR-362-3p Inhibits Migration and Invasion of Human Gastric Cancer Cells by Its Target CD82.

AIM: This study was to investigate the effects and mechanisms of miR-362-3p on regulation of gastric cancer (GC) cell metastasis potential. METHODS: We detected miR-362-3p level in GC and adjacent normal tissues and investigated the relationship with clinicopathological factors. Next, we analyzed the level of miR-362-3p expression and CD82 in different differentiated GC cells compared with a normal gastric mucosa cell by RT-PCR and Western blot. Dual-luciferase reporter assay and Western blot confirmed a direct interaction between miR-362-3p and CD82 3'UTR. After miR-362-3p and CD82 were silenced in GC cells, we compared the transfected GC cells migration and invasion capacity by transwell assay. In addition, we detected the effects on cells angiogenesis by tube formation assay. Western blot was used to detect the impact of CD82 and miR-362-3p on epithelial-to-mesenchymal transition markers in treated GC cells. RESULTS: Level of miR-362-3p expression was much higher in GC cells than in normal gastric mucosa cell, and miR-362-3p expression negatively correlated with CD82 mRNA expression in these cell lines. Furthermore, miR-362-3p expression induced [corrected] GC cell metastasis capacity by suppression of CD82 expression. Level of miR-362-3p may mediate E-cadherin, N-cadherin, and vimentin expression in GC cells. CONCLUSION: This study illuminated that downregulation of miR-362-3p along with the upregulation of CD82 in GC cells resulted in the inhibition of GC migration and invasion. Thus, our results suggested that miR-362-3p or CD82 can be exploited as a new potential target for control of GC in the future.

[Fracture reliability of zirconia all-ceramic crown according to zirconia coping design].

OBJECTIVE: To study the fracture resistance and characteristics of the bi-layer zirconia all ceramic crowns according to the zirconia coping design using various experimental methods and to compare the results of the in vitro test with the clinical evaluation. METHODS: The bi-layer zirconia all ceramic crowns were fabricated by the same method as used in clinical practice. Two different coping designs with/without zirconia marginal collar were used. All the samples were cemented onto corresponding resin dies. All the specimens were tested in the 2 groups with/without zirconia collar. The fracture load test was performed on 10 crowns from each group. Fracture strength was tested with a universal testing machine. The fracture modes and features of the failed crowns were observed with an integrated microscope and a field emission scanning electron microscope. RESULTS: The zirconia collar group showed higher fracture load than the group without zirconia collar. All the zirconia crowns failed with porcelain failure and without zirconia coping broken. The porcelain fracture modes were crack, chipping and delamination. The distribution of the different fracture modes in the groups was the same. CONCLUSION: The bi-layer zirconia crown with 2 mm zirconia marginal collar showed more fracture strength under once load. The fracture modes of the test specimens were the same as the clinical fracture bi-layer zirconia crowns, showing porcelain chipping and delamination.

[Expression of BRCA1 and WWOX and their clinicopathologic implication in breast carcinomas occurring in young women].

OBJECTIVE: To explore the clinicopathologic characteristics and biological markers of breast carcinomas in young women. METHODS: Immunohistochemical SP method was used to study breast cancer susceptibility gene (BRCA1) and WWOX in breast carcinomas of patient ≤ 35 years of age (107 cases) and ≥ 60 years of age (112 cases). The findings were correlated with clinicopathological features. In addition, PCR amplification and direct sequencing were performed to detect the BRCA1 gene mutation of exons 2 and 20 using fresh frozen tissue samples in other 10 patients who were ≤ 35 years of age. RESULTS: The positive rate of BRCA1 protein expression was higher in the young age group [65.4% (70/107)] than that of the old age group [35.7% (40/112)]. ER, PR, HER2, and WWOX protein expression and proliferation marker Ki-67 were no statistically different in the two groups (all P > 0.05). BRCA1 expression was significantly correlated with pTNM and axillary lymph node metastasis (both P < 0.05), but not with ER, PR, HER2 and WWOX protein expression (all P > 0.05). Ki-67 and histological grading showed no statistical correlation (P > 0.05). WWOX protein expression showed no correlation with clinicopathologic characteristics (all P > 0.05). Mutation of exons 2 and 20 of the BRCA1 gene was not detected in any of 10 cases studied. CONCLUSION: BRCA1 cytoplasmic expression statistically correlates with the development and prognosis of breast cancer of young patients.

[Spatial-temporal Variations and Pollution Assessment of Heavy Metals in Sediments of Qionghai Lake in Xichang City].

Based on the analysis of the total concentrations of 10 metals in the sediment core and total concentrations and chemical fractions of seven metals in the surface sediments of Qionghai Lake in Xichang City, Sichuan Province, the spatial-temporal characteristics of metal accumulation and pollution over the past century and the potential ecological risk of metals in surface sediments were studied. Before the 1970s, metal concentrations in the sediment core were stable. The total concentrations of Al, Fe, K, and Cr in the sediment core exhibited visible peaks in the 1970s, which were related to the enhanced input of fine-grained topsoil caused by increasing precipitation, lake reclamation, and deforestation. Since the 1990s, the total concentrations of Al, Fe, K, and Cr decreased with the reduced topsoil erosion, whereas the total concentrations of As, Cd, Cu, Pb, and Zn gradually increased or remained stable. The enrichment factor results showed that Cd, Pb, and Zn were the main contaminants, with Cd as the typical contaminant in the sediment core. The Cd contamination started in the 1960s and has remained at a moderate level since the 1990s. In the surface sediments, the total concentrations of Cd were higher in the northwest lake area, and no visible spatial concentration trends of the other metals were displayed. The bioavailable fractions of Cd, Pb, and Zn accounted for 95%, 63%, and 48% of the total metal concentrations on average. Among the bioavailable fractions, Cd was mainly in the acid-soluble fraction, and Pb and Zn were mainly in the reducible and oxidized fractions. The bioavailable fractions of the other metals were less than 27%. The results of total concentrations and bioavailable fractions of metals revealed that Pb and Zn in the surface sediments were slightly or moderately contaminated, and Cd was moderately contaminated on average. Cd contamination was at a severe level in the northwest lake area. The concentrations of anthropogenic Cd, Pb, and Zn in the surface sediments estimated from the total and bioavailable concentrations were comparable (P>0.05), indicating that anthropogenic metals primarily existed in bioavailable fractions in the sediment. Integrating the assessment results from sediment quality guidelines, potential ecological risk index, and chemical forms of metals, Cd in surface sediments may pose a high ecological risk, whereas the other metals has a low ecological risk.

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics.

Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. Methods: The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. Results: A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. Conclusion: The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

Different expression patterns of CEACAM1 and its impacts on angiogenesis in gastric nonneoplastic and neoplastic lesions.

OBJECTIVE: This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions. METHODS: CEACAM1 and TGF-ß expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry. RESULTS: There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-ß was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-ß coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05). CONCLUSIONS: CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-ß increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.

CD20-positive subcutaneous panniculitis-like T-cell lymphoma presenting as polycranial neuropathy: A CARE-compliant case report and literature review.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma(SPTCL) is a very rare cytotoxic T-cell skin lymphoma involving subcutaneous tissue, and mainly affects young females. T-cell phenotype is characterized by CD3+, CD8+, and CD4-. SPTCT with polycranial neuropathy has rarely been described. SPTCL is believed to show an indolent clinical course unless patients develop haemophagocytic syndrome or sudden respiratory failure. Its treatment has not been established yet. CASE PRESENTATION: We report a case of intractable SPTCT in a 66-year-old woman with multiple cranial nerve palsies and diabetes. She showed involvement of the bilateral facial nerve, left trigeminal nerve, left auditory nerve, and right oculomotor nerve. The single inconspicuous skin lesion in the trunk presented with an erythematous nodule with a diameter of <5 cm and a slightly pink infiltrated plaque. Electromyography revealed bilateral damage to the facial nerve. Differential immunohistochemical characteristics were observed. Immunohistochemistry demonstrated diffuse CD20 positivity. Cerebral spinal fluid analysis revealed elevated protein levels of 0.92 (0.15-0.45) g/L. Her condition regressed severely over time. She was treated with chemotherapy but died 10 months later, the probable cause of death was lung involvement. CONCLUSION: The patient's involvement with the central nervous system may be associated with positivity for CD20. Molecular biomarkers may act as therapeutic targets for SPTCL.

Inhibitor of differentiation is overexpressed with progression of benign to malignant lesions and related with carcinoembryonic antigen-related cell adhesion molecule 1 distribution in mammary glands.

The purpose of the study was to investigate the expression and association of inhibitor of differentiation (Id-1) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in benign, premalignant, and malignant lesions of human mammary glands. The study included 97 cases of benign, premalignant, and malignant lesions of human mammary glands including normal terminal duct lobular units, usual ductal hyperplasia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma that were surgically excised at the Second Hospital of Shangdong University. Immunohistochemistry was used to determine the expression of Id-1 and CEACAM1. The Id-1 expression was increased with the progression of benign to malignant transformation (P < .05) and positively related with CEACAM1 different expression patterns (r = 0.279, P < .01) in benign, premalignant, and malignant lesions: apical membranous staining in benign, and cytoplasmic and uniform membranous staining in premalignant and malignant lesions. A positive correlation was found between Id-1 expression and morphologic classification of benign to premalignant and malignant lesions (r = 0.641, P < .0001). The CEACAM1 expression patterns showed a significance between benign, premalignant, and malignant lesions (P < .05). The Id-1 expression is increased with the progression of benign to malignant transformation and promotes the CEACAM1 expression; the CEACAM1 expression patterns are changed by movement from apical membrane to bilateral membrane and cytoplasm. That the Id-1 overexpression promotes the transformation of CEACAM1 expression patterns may occur at the early stage in the breast carcinogenesis; and the Id-1 should be regarded as the transforming factor, which may regulate the transformation of CEACAM1 expression patterns.

Nuclear and cytoplasmic Id-1 expression patterns play different roles in angiogenesis and lymphangiogenesis in gastric carcinoma.

The purpose of the study was to investigate the expression and impact of Id-1 (inhibitor of differentiation) on tumor progression, angiogenesis, and lymphangiogenesis in gastric adenocarcinoma. The study included 97 cases of gastric adenocarcinoma, which were surgically excised at the Second Hospital of Shandong University. Immunohistochemistry was used to detect the Id-1 expression, and dual-labeling immunohistochemistry was used to evaluate the microvessel density (MVD) and lymphatic vessel density (LVD). The Id-1 protein was mainly expressed with nuclear staining in well-differentiated carcinoma, but with cytoplasmic staining in moderately and poorly differentiated carcinoma, which showed a significant difference (P < .0001). Moreover, the expression patterns had different and crucial effects on angiogenesis and lymphangiogenesis. Nuclear staining of Id-1 inhibited angiogenesis, but cytoplasmic staining promoted angiogenesis (MVD, 110.57 ± 32.32 vs 141.45 ± 55.60) (P < .05). Consistent with their roles in angiogenesis, the nuclear and cytoplasmic expressions of Id-1 had similar effects on lymphangiogenesis: nuclear expression inhibited and cytoplasmic expression promoted lymphangiogenesis (LVD, 2.62 ± 1.03 vs 4.05 ± 2.04) (P < .05). Microvessel density and LVD showed no significant difference in low-and high-Id-1 expression groups (P > .05). Aberrant expression of Id-1 from nuclear to cytoplasm is accompanied with tumor malignant progression, which promotes angiogenesis and lymphangiogenesis; and Id-1 should be developed as a target for gastric carcinoma therapy.

[Roles of PYK2 and caveolin-1 in alcoholic cardiomyopathy and the effect of drug intervention].

OBJECTIVE: To explore the protein expressions of PYK2 (protein-rich tyrosine kinase-2) and caveolin-1 in alcoholic cardiomyopathy (ACM) dog model and the effect of early drug intervention. METHODS: A total of 28 adult dogs were randomly divided into 4 groups: (i): alcohol-fed; (ii): alcohol plus valsartan, an angiotensin receptor blocker (ARB); (iii): alcohol plus carnitine; (iv): control group. At Month 6, the cardiac functions of all animals were evaluated by echocardiography. The concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in cardiac tissue were detected by chronometry. The protein expressions of collagen types I and III were determined by ELISA (enzyme-linked immunosorbent assay) while those of PYK2 and caveolin-1 evaluated by immunohistochemistry. The internal relationship of PYK2, caveolin-1, MDA and collagen types I & III was analyzed. RESULTS: Compared with the control group, the contents of SOD and GSH-Px significantly decreased in the alcohol, valsartan and carnitine groups while MDA significantly increased in the alcohol and carnitine groups. The relative contents in each group were as follows: MDA [alcohol: (28 ± 5) U/mg Pro; valsartan: (33 ± 13) U/mg Pro; carnitine: (33 ± 10) U/mg Pro], GSH-Px [alcohol: (188 ± 37) U/g Pro; valsartan: (362 ± 29) U/g Pro; carnitine: (282 ± 29) U/g Pro and MDA [alcohol: (19.4 ± 3.0) nmol/mg Pro; carnitine: (10.8 ± 2.1) nmol/mg Pro]. Compared with the control group, the concentration of collagen typeI significantly increased in the alcohol, valsartan and carnitine groups. In the alcohol-fed group, the protein expression of PYK2 gradually increased with the progression of ACM while that of caveolin-1 stayed at a low level. Through the interventions of valsartan and carnitine, the protein expression of PYK2 significantly increased while that of caveolin-1 significantly decreased (all P < 0.01). CONCLUSION: Alcohol promotes the myocardial oxidative stress and fibrosis through an elevated expression of PYK2 and a lowered expression of caveolin-1. Then a deterioration of cardiac structures and functions occur.

[Effect of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy].

OBJECTIVE: To evaluate the effects of valsartan and carnitine on cardiomyocyte Calpain-1 and Bcl-xl expressions of dogs with chronic alcohol intake-induced cardiomyopathy. METHODS: Dogs were randomly assigned into 4 groups (n = 7 each): (1) alcohol fed (free access to 5%, 1(st) week; 10% 2(nd) week; 500 ml 25% bolus plus free access to 5% from 3 to 24 weeks, A); (2) alcohol + valsartan (5 mg×kg(-1)×d(-1), B); (3) alcohol + carnitine (300 mg×kg(-1)×d(-1), C); (4) Control (D). After six months, all animals were assessed for left ventricular (LV) function by echocardiography. The Bad and Bcl-xl protein expressions were evaluated by immunohistochemistry. The expression of Calpain-1 protein was determined with Western blot. Myocardial morphology was quantified on HE stained slices and under electron microscopy. The terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) was performed for apoptosis analysis. RESULTS: Compared with group D, LVEDD and LVESD were significantly increased while EF and FS significantly decreased in group A. In alcohol fed group, expressions of Bad and Calpain-1 protein were significantly increased while Bcl-xl protein expression was downregulated, all changes could be significantly attenuated by intervention with valsartan and carnitine (all P < 0.05). CONCLUSION: These data suggest that alcohol could promote cardiac myocyte apoptosis, reduce cardiac function and aggravate myocardial remodeling which valsartan and carnitine could reduce alcoholic cardiomyopathy by downregulating Calpain-1 and Bad protein expression and upregulating expression of Bcl-xl protein.

Mineral Composition and Its Control on Nanopores of Marine-Continental Transitional Shale from the Ningwu Basin, North China.

There is a large difference between the sedimentary environment and maturity of organic matter between marine shale and marine-continental transitional shale. It is of great significance to discuss the effect of inorganicminerals on the pores for marine-continental transitional shale gas exploration. In this study, scanning electron microscopy (SEM), low temperature liquid nitrogen adsorption and Xray diffraction (XRD) were conducted on eight marine-continental transitional shale samples from the Ningwu Basin, Shanxi Province, China. The pore structure differences in the different minerals were discussed, and the relationship between the mineral content and pore parameters was analysed. The results show that the mineral composition of shale is dominated by clay minerals, quartz, carbonate minerals and a small amount of pyrite. The clay minerals content is between 39.5% and 77.0%, with an average of 59.9%. The quartz content ranges from 21.8% to 47.8%, with an average of 31.9%. The carbonate minerals content in shale is between 0.6% and 23.9%, and the average is 6.3%. The clay minerals are composed of mixed illite-montmorillonite layer, kaolinite and chlorite. The content of mixed illite-montmorillonite layer is between 13.8% and 27.4%, with an average of 20.4%. The kaolinite content ranges from 57.0% to 86.2%, with an average of 76.0%. The content of chlorite is between 0 and 15.6%, with an average of 5.7%. The types of pores are mainly intergranular pores and interlaminar pores, which are mostly presented as slit and parallel plates. The mixed illite-montmorillonite layer contributes more to the specific surface area, which is favourable for shale gas adsorption. The pores in kaolinite are more developed than those of the mixed illite-montmorillonite layer, but the pore diameter is relatively large. The quartz granule has a complete crystal type, and intergranular pores with a large pore size are often developed at the mineral contacts. Compared with clay minerals and quartz, the pore development in the carbonate minerals is relatively poor and develops more micro-fractures. The pyrite contributes a certain number of intergranular pores and mold pores.

APCCDC20-mediated degradation of PHD3 stabilizes HIF-1a and promotes tumorigenesis in hepatocellular carcinoma.

CDC20 regulates cell cycle progression by targeting key substrates for destruction, but its role in hepatocellular carcinoma (HCC) tumorigenesis remains to be explored. Here, by using weighted gene co-expression network analysis (WGCNA), we identified CDC20 as a hub gene in HCC. We demonstrated that CDC20 expression is correlated with HIF-1 activity and overall survival (OS) of clinic HCC patients. The activity of HIF-1 is regulated by the stability of HIF-1a subunit, which is hydroxylated by oxygen-dependent prolyl hydroxylase enzymes, the PHDs. In addition, we show that genetic ablation or pharmacological inhibition of CDC20 can accelerate the degradation of HIF-1a and impair VEGF secretion in HCC cells. Mechanistically, we found that CDC20 binds to the destruction-box (D-box) motif present in the PHD3 protein to promote its polyubiquitination and degradation. The depletion of endogenous PHD3 in CDC20 knockdown HCC cells greatly attenuated the decline of HIF-1a protein and restored the secretion of VEGF. In contrast, overexpression of a non-degradable PHD3 mutant significantly inhibited the proliferation of HCC cells both in vitro and in vivo. Collectively, our findings indicate that CDC20 plays a crucial role in the development of HCC by governing PHD3 protein.

Lymphangiogenesis in gastric carcinoma correlates with prognosis.

Lymphatic metastasis is an important way that gastric carcinomas can spread. However, little is known about the mechanisms of lymphangiogenesis and its clinical significance in gastric carcinomas. In the present study, lymphatic vessel density (LVD), VEGF-C expression, and proliferative activity of lymphatic endothelium were determined in human gastric carcinomas and xenografts of gastric cancer cells in nude mice. The development of lymphangiogenesis and its correlation with patient prognosis were investigated. The results showed that lymphatic vessels were observed mainly in peripheral tumour tissue with significantly (p < 0.05) higher P-LVD (peri-tumoural-LVD) than I-LVD (intra-tumoural-LVD). The expression of VEGF-C was heterogeneous within tumours, with a significantly higher expression (immunostaining score) at the margin than at the tumour centre (p < 0.05). A significant correlation was found between VEGF-C expression at the margin (but not at the centre) and P-LVD (r = 0.72, p < 0.01). High proliferative activity of lymphatic endothelium was also observed in the peripheral tissues, with a significant correlation between proliferative activity of lymphatic endothelium and VEGF-C expression (p < 0.05). These data imply that the increased lymphatics may have been newly formed following stimulation by VEGF-C. High VEGF-C expression at the margin of gastric carcinomas could induce lymphangiogenesis in the peri-tumoural stroma and contribute to the increased P-LVD. The data from mice tumour xenografts also suggested that VEGF-C produced from the transplanted gastric carcinoma cells could induce lymphangiogenesis around them. In patients, VEGF-C expression at tumour margins was associated with nodal metastasis, lymphatic vessel invasion, poor recurrence-free survival, and poor overall survival, and could serve as an independent predictor for patients with gastric carcinoma.

CMIP SNPs and their haplotypes are associated with dyslipidaemia and clinicopathologic features of IgA nephropathy.

The relationship between serum lipid profiles and related clinicopathologic features of IgA nephropathy (IgAN) and c-Maf-inducing protein (CMIP) gene polymorphisms is unclear. The present study was designed to examine the effect of CMIP single-nucleotide polymorphisms (SNPs) on dyslipidaemia and clinicopathologic features of IgAN. Clinical and pathological data from patients with IgAN diagnosed at the First Affiliated Hospital of Guangxi Medical University were collected. DNA was extracted from blood samples. CMIP rs2925979 and CMIP rs16955379 genotypes were determined by PCR and direct sequencing. Among 543 patients, 281 had dyslipidaemia (51.7%). Compared with the non-dyslipidaemia group, the dyslipidaemia group exhibited higher blood pressure, blood urea nitrogen, uric acid, and body mass index; higher prevalence of oedema, haematuria, tubular atrophy, and interstitial fibrosis; and lower albumin and estimated glomerular filtration rate. In the dyslipidaemia group, the frequency of C allele carriers was higher than that of non-C allele carriers for rs16955379. Multivariate linear regression analysis showed that total cholesterol, low-density lipoprotein and high-density lipoprotein were associated with rs16955379C allele carriers. Apolipoprotein B was associated with A allele carriers of rs2925979. Linkage disequilibrium was observed between rs16955379 and rs2925979, and rs2925979G-rs16955379T was the most common haplotype. The frequencies of the four CMIP SNP haplotypes differed between dyslipidaemia and non-dyslipidaemia groups in IgAN (P<0.05, for all above). Dyslipidaemia is a common complication in IgAN patients, and those with dyslipidaemia present poor clinicopathologic features. CMIP SNPs and their haplotypes are closely correlated with the occurrence of dyslipidaemia and clinicopathologic damage in IgAN patients.