Multi-regional sequencing reveals the genetic and immune heterogeneity of non-cancerous tissues in gastric cancer.

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.

A novel somatic mutation in POLE exonuclease domain associated with ultra-mutational signature and MMR deficiency in endometrial cancer: a case report.

BACKGROUND: Defect in proofreading exonuclease activity of polymerases epsilon and delta (Pols ε and δ) leads to mutagenesis and genomic instability and has been described in several cancer types. Somatic POLE exonuclease domain mutations (EDMs) have been reported in 7-12% endometrial cancers (ECs) and defined a subgroup of endometrial cancers with ultrahigh somatic mutation frequencies, high tumor infiltrated lymphocytes and favorable outcomes. CASE PRESENTATION: Herein, we presented a novel somatic mutation in POLE exonuclease domain associated with ultra-mutational signature and MMR deficiency in endometrial cancer. A novel POLE EDM (p.T278K) was found by a 11-gene NGS panel. The MSS status detected by the MSI test was inconsistent with the dMMR status by IHC. The loss of MSH6 expression in the tumor could be interpreted by the two nonsense mutations (p.E1234* and p.E1322*) of the MSH6 gene which may lead to truncated proteins. The T278K mutation was pathogenic identified by a 602-gene NGS panel with 27.3% of C > A substitution, 0.6% of indels, 0.6% of C > G substitution and a high TMB of 203.8 mut/Mb. CONCLUSIONS: We report an endometrial cancer patient harbored a novel somatic POLE T278K mutation. This mutation was a novel pathogenic POLE EDM should be considered as "POLE (ultramutated)" in clinical practice for the molecular classification of EC.

Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial.

Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.

Phylogenetic analysis of porcine circovirus 4 in Henan Province of China: A retrospective study from 2011 to 2021.

Porcine circovirus 4 (PCV4), a novel circovirus, was first discovered in April 2019 in Hunan Province of China. At present, PCV4 infection has been detected in China and South Korea. However, until 2019, there was little information about its circulating status and genetic characteristics. To further clarify the origin and prevalence of PCV4, a total of 152 clinical samples collected from 49 different swine farms of 15 cities in Henan Province of China from 2011 to 2021 were tested for the presence of PCV4 by qPCR, and the complete genome of PCV4 strains was amplified from the positive samples and sequenced. Among these samples, 45.39% (69/152) were positive for PCV4 and 86.67% (13/15) of the cities and 67.35% (33/49) of the swine farms were positive for PCV4. The genome sequences of 15 PCV4 strains were obtained, of which two PCV4 strains (HN-ZMD-201212 and HN-XX-201212) were achieved from archival samples in 2012, indicating that PCV4 has been circulating for at least 10 years in Henan Province of China. The phylogenetic analysis showed that 15 PCV4 strains in our study together with PCV4 strain HNU-AHG1-2019 were clustered into an identical but separate evolutionary branch, with genomic identity ranging from 98.2% to 98.8%. Our research further provides significant epidemiological information on PCV4 in China, which will help understand the origin and genetic characteristics of this new virus.

Prevalence and pattern of refractive error and visual impairment among schoolchildren: the Lhasa childhood eye study.

BACKGROUND: Early and effective ocular screening may help to eliminate treatable eye disorders. The Lhasa Childhood Eye Study (LCES) revealed the particular prevalence of refractive error and visual impairment in grade one schoolchildren (starting age of 6 years old) in Lhasa. METHODS: This is a cross-sectional part of school-based cohort study. One thousand nine hundred forty-three children were enrolled (median age, 6.78 years, range, 5.89 to 10.32). Each child underwent general and ocular examinations, including logarithm of the minimum angle of resolution (logMAR) visual acuity, cycloplegic autorefraction, and slit-lamp biomicroscopy evaluation. Multivariate and correlation analyses were performed to evaluate the association between refractive error with gender and ethnics. RESULTS: The prevalence of visual impairment (logMAR visual acuity ≥0.3 in the better-seeing eye) of uncorrected, presenting and best-corrected visual acuity (BCVA) was 12.2, 11.7 and 2.7%, respectively. Refractive error presented in 177 (78.0%) out of 227 children with bilateral visual impairment. Myopia (spherical equivalent refractor [SER] ≤ - 0.50 diopter [D] in either eye) was present in 4.7% children when measured after cycloplegic autorefraction. Hyperopia (SER ≥ + 2.00 D) affected 12.1% children. Hyperopia was significantly associated with female gender (P<0.001). Astigmatism (cylinder value ≤ - 0.75 D) was present in 44.8% children. In multivariate regression and correlation analysis, SER had no significant difference between ethnic groups. CONCLUSION: The Lhasa Childhood Eye Study is the first school-based cohort study to reveal the prevalence and pattern of refractive error and visual impairment in Lhasa. Effective strategies such as corrective spectacles should be considered to alleviate treatable visual impairment.

Prevalence and risk factors of refractive error in Qinghai, China: a cross-sectional study in Han and Tibetan adults in Xining and surrounding areas.

BACKGROUND: Our study aimed to explore the prevalence and risk factors of refractive error (RE) in Han and Tibetan population aged 50-79 years in Xining and surrounding areas in Qinghai Province on Qinghai-Tibet Plateau. METHODS: As part of the China National Health Survey, our cross-sectional study compared the age-adjusted prevalence of RE in Han and Tibetan older adults aged 50-79 years in Xining and surrounding areas. A multivariate logistic regression model was used to identify risk factors for myopia and hyperopia. RESULTS: Among 769 Han participants and 476 Tibetan participants, the age-adjusted prevalence of myopia (spherical equivalent (SE) < - 0.5D), hyperopia (SE > + 0.5D), high myopia (SE < -6.0D) and astigmatism (cylindrical equivalent > = 0.5D) is 28.56, 22.82, 2.80, and 69.38%. Han participants have higher age-adjusted prevalence of myopia (32.93% vs 21.64%, p < 0.001), high myopia (3.93% vs 1.02%, p = 0.001) and astigmatism (72.14% vs 64.94%, p = 0.021) compared to Tibetan participants. Being Tibetan is the protective factor of myopia compared to being Han (OR 0.58, 95%CI 0.42-0.79, p < 0.001). Older age (p = 0.032), longer time length in rural area (p = 0.048), undergraduate/graduate education level (p = 0.031), lighter active level (p = 0.007) and lower BMI (p = 0.015) are risk factors for myopia. Older age (all p < 0.001) and pterygium status of the same eye (p = 0.013) also increase the hyperopia risk. CONCLUSIONS: Our study found an overall prevalence of myopia of 28.56% in Xining and surrounding areas in adults older than 50 years. Han population has higher myopia risk than Tibetan population. More medical and social resources should be allocated to improve the vision and life quality of older adults.

Simultaneous detection and differentiation of porcine circovirus 3 and 4 using a SYBR Green І-based duplex quantitative PCR assay.

Porcine circovirus 4 (PCV4) was a novel circovirus identified from diseased pigs in 2019 in Hunan Province, China, and PCV3 and PCV4 co-infection has been reported. In order to detect and differentiate PCV3 and PCV4 simultaneously, the SYBR Green І-based duplex quantitative PCR (qPCR) assay was established in the present study. The two viruses could be easily distinguished by different Tm values: 86.5°C for PCV3 and 79°C for PCV4, while other porcine pathogens did not shown specific melting peaks. The detection limits of this duplex qPCR assay were 51.7 copies/µL for PCV3 and 67.7 copies/µL for PCV4, and both of the intra-assay and inter-assay of the CV analysis of this assay were less than 2.0 %. Sixty-four clinical samples from 22 different swine farms were screened by the duplex qPCR assay. The results showed that the positive detection rate of PCV3 was 37.5 % (24/64) and PCV4 was 34.38 % (22/64), and PCV3 and PCV4 co-infection rate was 17.19 % (11/64). The detection rate of the duplex qPCR assay was higher than that of the conventional PCR assay. The duplex qPCR was of high sensitivity and specificity, being able to provide technical support for clinical detection, differential diagnosis and control of PCV3 and PCV4.

Detection and genetic characteristics of porcine bocavirus in central China.

To investigate the epidemic profile and genetic diversity of porcine bocavirus (PBoV), 281 clinical samples, including 236 intestinal tissue samples and 45 fecal samples were collected from diarrheic piglets on 37 different pig farms in central China, and two SYBR Green I-based quantitative PCR assays were developed to detect PBoV1/2 and PBoV3/4/5, respectively. One hundred forty-eight (52.67%) of the 281 clinical samples were positive for PBoV1/2, 117 (41.63%) were positive for PBoV3/4/5, 55 (19.57%) were positive for both PBoV1/2 and PBoV3/4/5, and 86.49% (32/37) of the pig farms were positive for PBoV. Overall, the prevalence of PBoV was 74.73% (210/281) in central China. Subsequently, nearly full-length genomic sequences of two PBoV strains (designated CH/HNZM and PBoV-TY) from two different farms were determined. Phylogenetic analysis demonstrated that the two PBoV strains obtained in this study belonged to the PBoV G2 group and had a close relationship to 10 other PBoV G2 strains but differed genetically from PBoV G1, PBoV G3, and seven other bocaviruses. CH/HNZM and PBoV-TY were closely related to the PBoV strain GD18 (KJ755666), which may be derived from the PBoV strains 0912/2012 (MH558677) and 57AT-HU (KF206160) through recombination. Compared with reference strain ZJD (HM053694)-China, more amino acid variation was found in the NS1 proteins of CH/HNZM and PBoV-TY. These data extend our understanding of the molecular epidemiology and evolution of PBoV.

Molecular detection and phylogenetic analysis of Porcine circovirus 4 in Henan and Shanxi Provinces of China.

Porcine circovirus 4 (PCV4), a new circovirus with a distinct relationship to other circoviruses, was identified in 2019 in several pigs with severe clinical disease in Hunan Province, China. To investigate the epidemic profile and genetic diversity of the virus, 63 clinical samples were collected from 24 different pig farms in 14 cities in Henan and Shanxi Provinces, China, between February 2018 and December 2019, and the partial Cap gene of PCV4 was amplified by PCR. Among the 63 samples, 16 (25.40%) were positive for PCV4, and 50% (12/24) of the pig farms were positive for PCV4. PCV4 was detected in samples from pigs with different clinical presentations. One PCV4 strain (Henan-LY1-2019) was sequenced in this study, and shared 98.4% genomic nucleotide identity with PCV4 strain HNU-AHG1-2019 (accession no. MK986820) detected on a pig farm in Hunan Province in 2019. A phylogenetic analysis based on the genomes of Henan-LY1-2019 and 31 reference strains showed that the Henan-LY1-2019 strain together with PCV4 strain HNU-AHG1-2019 was grouped in a relatively independent sub-branch, and separated from other viruses in the genus Circovirus. The results of this study extend our understanding of the molecular epidemiology of PCV4.

Dysregulation of MiR-30a-3p/Gastrin Enhances Tumor Growth and Invasion throughSTAT3/MMP11 Pathway in Gastric Cancer.

BACKGROUND: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically. METHODS: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis. RESULTS: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p<0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study. CONCLUSION: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.

Characteristics of the spike and ORF3 genes of porcine epidemic diarrhea virus in Henan and Shanxi provinces of China.

To investigate the epidemic characteristics of porcine epidemic diarrhea virus (PEDV), 135 clinical samples (including intestinal tissues and feces) were collected from diseased piglets during outbreaks of diarrhea from 2015 to 2019 on farms in Henan and Shanxi provinces of China where swine had been immunized with attenuated PEDV (CV777). A total of 86 clinical samples (86/135, 63.7%) were positive for PEDV by RT-PCR, and subsequently, the complete spike (S) and ORF3 genes of 32 PEDV samples were sequenced. Phylogenetic analysis showed that the 32 PEDV strains obtained in this study belonged to group 2 (pandemic variant strains) and had a close relationship to 17 Chinese strains after 2010, two South Korean strains (KNU-1305 and KNU-1807), three American strains (PC22A-P140.BI, USA/Colorado/2013, and USA/OK10240-6/2017) and a Mexican strain (PEDV/MEX/QRO/02/2017), but differed genetically from a South Korean strain (SM98), a European strain (Br1/87), a Chinese strain (LZC), and a vaccine strain (CV777). G2-a subgroup strains were the dominant pandemic variant strains circulating in Henan and Shanxi provinces of China. Furthermore, a cross-recombination event was identified in the S region of the SX/TY2/2017 strain, and the putative parental strains were the epidemic strains CH/GDGZ/2012 and CH/YZ1/2015, identified in China in 2012 and 2015, respectively. These results provide further information about PEDV evolution, which could improve our understanding of the circulation of PEDV in Henan and Shanxi provinces. This information will also be helpful for developing new strategies for prevention and control of variant strains.

Development of a duplex SYBR Greenâ based real-time PCR assay for detection of porcine epidemic diarrhea virus and porcine bocavirus3/4/5.

The duplex real-time PCR assay based on SYBR Green І was developed for detection of porcine epidemic diarrhea virus (PEDV) and porcine bocavirus (PBoV) 3/4/5 genotypes simultaneously. Two pairs of specific primers were designed targeting the N gene sequence of PEDV and VP1 gene sequence of PBoV3/4/5. PEDV and PBoV3/4/5 could be distinguished by their different melting temperatures (Tm) in one sample. The Tm value of PEDV was 83.5 °C, and the Tm value of PBoV3/4/5 was 78.5 °C, while other swine pathogens showed no specific melting peaks. The detection limits of this assay were 10 copies/µL for both PEDV and PBoV3/4/5. A total of sixty-three intestinal tissue samples were collected from piglets suffering from diarrhea, and the viral nucleic acids detected and identified by the real-time PCR assay and conventional PCR assay. The duplex real-time PCR detection results showed that the prevalence of PEDV and PBoV3/4/5 was 85.7% and 46%, respectively, and the co-infection rate of the two viruses was 28.6%. These results indicated that this duplex real-time PCR assay was a sensitive, specific and reproducible method for differentiating PEDV and PBoV3/4/5 or their co-infection.

Simultaneous detection of classical swine fever virus and porcine circovirus 3 by SYBR green I-based duplex real-time fluorescence quantitative PCR.

In the present study, the SYBR green I-based duplex quantitative polymerase chain reaction (qPCR) was developed for simultaneous detection of classical swine fever virus (CSFV) and porcine circovirus 3 (PCV3). The assay was used to detect both CSFV and PCV3 in one sample by their distinct melting temperatures (melting peaks at 87°C for CSFV and 81.5 °C for PCV3), and no specific fluorescence signals were detected for other non-targeted porcine pathogens. The assay had a high degree of linearity (R2 > 0.998) with the detection limits of 23 copies/µL for CSFV and 36 copies/µL for PCV3, and exhibited high repeatability and reproducibility with a low coefficient of variation below 2.0% in both intra- and inter-assay. In this study, 130 clinical samples collected from sick pigs in the field were tested by this assay with the positive rates of 9.23% (12/130) for CSFV and 21.54% (28/130) for PCV3 respectively, and the positive rate of CSFV and PCV3 co-infection was 6.92% (9/130). Our results showed that the developed method was a reliable diagnostic tool to monitor and survey CSFV, PCV3 and CSFV/PCV3 co-infection in the field.

Pyruvate kinase M2 contributes to cell growth in gastric cancer via aerobic glycolysis.

Pyruvate kinase M2 (PKM2) serves as a key enzyme that promotes aerobic glycolysis. This study investigated the function of PKM2 in tumor growth and maintenance in gastric cancer (GC). Histological staining was applied to detect PKM2 expression in GC tissues. PCR and western blotting were used to measure PKM2 expression in GC cells. PKM2 was knocked down to examine the biological behavior of tumors, glycometabolism, and apoptosis. PKM2 was upregulated in GC tissues (65%, 34/52) compared with that in adjacent normal tissues (27%, 10/37). Moreover, PKM2 knockdown inhibited proliferation of BGC823 GC cells, and elevated PKM2 levels were associated with poor survival of GC patients. Furthermore, knockdown of PKM2 altered the biological behavior of BGC823 cells through induction of apoptosis. In conclusion, the results of this study indicated that inhibition of PKM2 could represent a novel strategy for gastric cancer treatment.

Development of a TB green II-based duplex real-time fluorescence quantitative PCR assay for the simultaneous detection of porcine circovirus 2 and 3.

Porcine circovirus 3 (PCV3), as a newly emerged circovirus, is widely distributed in pig populations worldwide. Co-infection of PCV2 and PCV3 has been reported frequently in clinical samples. In the present study, a TB Green II-based duplex real-time polymerase chain reaction (qPCR) was developed to rapidly and differentially detect PCV2 and PCV3. The assay specifically detected PCV2 and PCV3, with no fluorescence signals being detected for other non-targeted pig pathogens. The duplex qPCR showed a high degree of linearity (R2 > 0.998), and its limits of detection were 10 and 78 copies/µL for PCV2 and PCV3, respectively. The duplex qPCR could detect and differentiate PCV2 (melting peaks at 85.5 °C) and PCV3 (melting peaks at 82.5 °C), and showed high repeatability and reproducibility, with intra- and inter-assay coefficients of variation of less than 2.0%. Fifty-six tissue samples from 18 pig farms were used to evaluate the duplex qPCR method. The results revealed infection rates of 66.07% (37/56) and 39.28% (22/56) for PCV2 and PCV3, respectively. The PCV2 + PCV3 co-infection rate was 39.28% (22/56). The developed method could be used as an efficient molecular biology tool for epidemiological investigations of PCV2 and PCV3.

Prevalence and risk factors for pterygium: a cross-sectional study in Han and Manchu ethnic populations in Hebei, China.

AIMS: To investigate the prevalence, ethnic differences and associated risk factors for pterygium in Han and Manchu populations aged 40-79 years in Hebei province, China. DESIGN: Cross-sectional study, as a part of the China National Health Survey. SETTING: Hebei province, China. PARTICIPANTS: A multistage cluster sampling method with urbanisation level-based stratification was used to select participants for this study. A total of 4591 individuals over 40 years were recruited for this study. Inclusive criteria: (1) residents who had been living in Hebei for more than 1 year; (2) Han individuals with both parents being Han, or Manchu individuals with both parents being Manchu; (3) underwent ophthalmic examinations and (4) information in the questionnaire was complete. MAIN OUTCOME MEASURES: Multiple logistic regression analysis was used to evaluate the association between pterygium prevalence and factors of interest. RESULTS: A total of 3790 individuals (2351 Hans and 1439 Manchus) met the study criteria, of which 248 were diagnosed with pterygium (6.5%). There was no significant difference between the prevalence rates in Hans (6.2%) and Manchus (7.2%) (p=0.232). Multivariate analysis revealed that the risk factors for grade 2 or higher pterygium were increasing age (p<0.001) and rural residence (OR 1.83; 95% CI 1.11 to 3.02; p=0.018), while the protective factors include gender (female) (OR 0.58; 95% CI 0.37 to 0.88; p=0.011), cigarette smoking (OR 0.53; 95% CI 0.34 to 0.83; p=0.005) and myopia (OR 0.50; 95% CI 0.33 to 0.77; p=0.002). Premature menopause (OR 2.66; 95% CI 1.05 to 6.72; p=0.038) increased the risk of grade 2 or higher pterygium in females, while higher high-density lipoprotein (HDL) (OR 1.94; 95% CI 1.08 to 3.47; p=0.027) was a risk factor of grade 2 or higher pterygium in males. CONCLUSION: The overall prevalence of pterygium in Han and Manchu population in Hebei, China was approximately 6.1%. There were no differences in the prevalence of pterygium between Hans and Manchus, and the race was not a risk factor. This is the first study to report on the positive association between premature menopause and pterygium in females and between higher HDL levels and pterygium in males.

Androgen receptor variant 12 promotes migration and invasion by regulating MYLK in gastric cancer.

Androgen receptor (AR) and its variants (AR-Vs) promote tumorigenesis and metastasis in many hormone-related cancers, such as breast, prostate and hepatocellular cancers. However, the expression patterns and underlying molecular mechanisms of AR in gastric cancer (GC) are not fully understood. This study aimed to detect the expression of AR-Vs in GC and explored their role in metastasis of GC. Here, the AR expression form was identified in GC cell lines and tissues by RT-PCR and qPCR. Transwell assays and experimental lung metastasis animal models were used to assess the function of AR in cell migration and invasion. Downstream targets of AR were screened by bioinformatics, and identified by luciferase reporter assays and electrophoretic mobility shift assays. AR-v12 was identified as the main expression form in GC cell lines and tissues. Different from full length of AR, AR-v12 was localized to the nucleus independent of androgen. Upregulation of AR-v12 in primary GC tissues was significantly associated with metastasis. Overexpression of AR-v12 promoted migration and invasion independent of androgen. Knockdown of AR-v12 inhibited migration and invasion in vitro, as well as metastasis in vivo. Furthermore, AR-v12, serving as a transcription factor, promoted metastasis through regulating the promoter activity of MYLK. In AR-v12 overexpressing cells, knockdown of MYLK inhibited cell migration and invasion, while in AR-v12 knocked-down cells, overexpression of MYLK promoted cell migration and invasion. Collectively, our study demonstrates that AR-v12 is highly expressed in GC tissues and promotes migration and invasion through directly regulating MYLK. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Epigenetic downregulation of MUC17 by H. pylori infection facilitates NF-κB-mediated expression of CEACAM1-3S in human gastric cancer.

BACKGROUND AND AIMS: Helicobacter pylori invades the mucosal barrier and infects the mucins of gastric epithelial cells. However, whether gastric carcinogenesis caused by H. pylori infection involves the membrane-bound mucins is unclear. This study explored the role of mucin 17 (MUC17) in gastric cancer (GC) associated with H. pylori infection. METHODS: The expression of MUC17 and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was examined in human GC cells and tissues with H. pylori infection. Gain- and loss-of-function assays were performed to assess the role of MUC17 in regulating CEACAM1 in H. pylori-infected GC cells. RESULTS: MUC17 was downregulated in H. pylori-infected GC cells and tissues in association with poor survival of GC patients. Downregulation of MUC17 was attributable to MUC17 promoter methylation mediated by DNA methyltransferase 1 (DNMT1) H. pylori-enhanced GC cell proliferation and colony formation associated with MUC17 downregulation. Gain- and loss-of-function assays showed that MUC17 inhibited the H. pylori-enhanced GC cell growth by preventing the translocation of H. pylori CagA into GC cells. Moreover, MUC17 downregulated the expression of CEACAM1 variant 3S (CEACAM1-3S) in GC cells and tissues with H. pylori infection. Additionally, MUC17 downregulated CEACAM1 promoter activity via attenuation of NF-κB activation in GC cells. CONCLUSIONS: MUC17 was epigenetically downregulated in GC with H. pylori infection. MUC17 inhibited H. pylori CagA translocation via attenuation of NF-κB-mediated expression of CEACAM1-3S in GC cells. Thus, MUC17 may serve as a valuable prognostic biomarker for H. pylori-associated GC.

Prevalence and risk factors of refractive error: a cross-sectional Study in Han and Yi adults in Yunnan, China.

BACKGROUND: Few studies have investigated the prevalence of refractive error (RE) in older adults in China, and most have focused on East China. Our study determined the prevalence and risk factors of RE in Han and Yi adults aged 40-80 years in rural and urban areas in Yunnan Province, Southwest China. METHODS: Our cross-sectional study is part of the China National Health Survey (CNHS). The age-adjusted prevalence rates of RE in Han and Yi adults aged 40-80 years in Yunnan were compared. We used a multivariate logistic regression model to identify risk factors for myopia and hyperopia. RESULTS: Among 1626 participants, the age-adjusted prevalence rates of myopia, hyperopia, high myopia and astigmatism were 26.35% (95%CI 24.01-28.70%), 19.89% (95%CI 18.16-21.61%), 2.64% (95%CI 1.75-3.53%), and 56.82% (95%CI 54.31-59.34%). Compared to the Yi population, the Han population had higher prevalence of myopia (31.50% vs 16.80%, p < 0.0001), high myopia (3.34% vs 1.31%, p = 0.049) and astigmatism (60.07% vs 50.67%, p = 0.026) but lower prevalence of hyperopia (16.58% vs 27.37%, p < 0.0001). In the multivariate logistic regression, individuals aged 45-49 (p < 0.001), 50-54 (p < 0.001), 55-59 (p = 0.014), and 60-64 years (p = 0.005) had a lower myopia risk than those aged 40-44 years, and individuals aged 50-54 (p = 0.002), 55-59, 60-64 and 65 years and older (all p < 0.001) had a higher hyperopia risk than those aged 40-44 years. Myopia was also associated with height (p = 0.035), time spent in rural areas (p = 0.014), undergraduate/graduate education level (p = 0.001, compared with primary school or lower education level) and diabetes (p = 0.008). The Yi population had a higher risk of hyperopia than the Han population (p = 0.025). Moreover, hyperopia was related to time spent in rural areas (p < 0.001) and pterygium (p = 0.019). CONCLUSIONS: Our study investigated the overall prevalence of RE in older adults in rural and urban areas of Southwest China. Compared to the Yi population, the Han population had a higher prevalence of myopia, high myopia and astigmatism but a lower risk of hyperopia. The prevalence of myopia in the Han population in underdeveloped Southwest China was similar to that of residents in East China or of Chinese Singaporeans under urban or rural settings.