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Objectives This study aimed to analyze the safety, efficacy, and application prospects of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperthyroidism.Methods Eight patients with primary hyperthyroidism who underwent ultrasound-guided glandular volume reduction between January 2021 and December 2022 were included in this study. Pre- and postablative examinations, including grayscale ultrasound, contrast-enhanced ultrasound (CEUS), laboratory examination, antithyroid drug (ATD) dosage, and quality of life (QoL) assessment via Thyroid-Specific Patient-Reported Outcome Short-Form (ThyPRO-39), were analyzed retrospectively. The main ultrasound follow-up times were 1, 3, 6, and 12 months after ablation. Thyroid function was reviewed 1 week after ablation, and the subsequent reexamination time was determined according to the patient’s specific test results and ATD adjustment. The final efficacy was comprehensively analyzed according to the patient’s medication status, thyroid function, thyroid volume, and QoL score.Results All 8 patients successfully received MWA for primary hyperthyroidism, and none of them experienced serious complications. By the end of the follow-up, 5 of the 8 patients had stopped taking ATDs, 3 of the 8 patients had reduced ATD dosages, and all of them maintained stable thyroid function. Although descriptive analysis was performed because of the small sample size, patients’ thyroid volume reduction, and obvious improvements in goiter symptoms, hyperthyroid symptoms, anxiety, etc., were observed during our follow-up.Conclusion Ultrasound-guided MWA for reducing thyroid gland volume in primary hyperthyroidism patients is a new, safe, and effective minimally invasive treatment method that is a good choice for patients who cannot or refuse traditional treatment methods.

Abstract Objective To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. Methods An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. Results The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p

BackgroundArecanut seed is an important traditional medicine in Southeast Asia. It has been presented in a clinical formula to treat osteoporosis (OP) in China. Arecanut seed is abundant in phenols. However, most of current studies mainly focused on estrogen-deficient osteoporosis (OP) model of arecanut seed phenols (ASP), there is still a lack of roundly research about molecular mechanism of ASP therapy on OP and its influence on in drug-induced bone loss.Materials and methodsTo explore potential molecular mechanisms and the effects of ASP on OP, network pharmacology, molecular docking methods and a retinoic acid-induced OP rat model were employed in this study. According to the network pharmacology method, OP related targets and ASP compound related targets were collected from databases to obtain hub targets and top active chemicals in ASP treating OP. The potential therapic pathways were also calculated. Binding capacities of top active chemicals to hub targets were analyzed by molecular dock assay. In the animal experiment, osteocalcin (OCN) levels and alkaline phosphatase (ALP) activity in serum of all the rats were determined. The views of bone section were stained to observe the bone micro-structure of ASP affects. Bone mineral density (BMD), cortical bone thickness (CBT), area ratio of bone cortex (CAR) and area ratio of bone trabecula (TAR) were obtained from micro computed tomography to evaluate the effectiveness of ASP on bone loss.ConclusionThree hub genes and three top active compounds were screened by network pharmacology analysis and they combined well with each other. ASP had positive effects on alleviating RA-induced bone loss by regulating the expression of the hub genes. Signals in IL-17 pathway were predicted and primarily verified being potential targets in ASP treating OP.

Summary: The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p

Summary: Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases. Methods: Between Jan 10, 2017, and Dec 31, 2020, the DMFN model was trained and validated using 1269 close-ups and 11,852 HFUS images from 1351 skin lesions. The monomodal convolutional neural network (CNN) model was trained and validated with the same close-up images for comparison. Subsequently, we did a prospective and multicenter study in China. Both CNN models were tested prospectively on 422 cases from 4 hospitals and compared with the results from human raters (general practitioners, general dermatologists, and dermatologists specialized in HFUS). The performance of binary classification (benign vs. malignant) and multiclass classification (the specific diagnoses of 17 types of skin diseases) measured by the area under the receiver operating characteristic curve (AUC) were evaluated. This study is registered with www.chictr.org.cn (ChiCTR2300074765). Findings: The performance of the DMFN model (AUC, 0.876) was superior to that of the monomodal CNN model (AUC, 0.697) in the binary classification (P = 0.0063), which was also better than that of the general practitioner (AUC, 0.651, P = 0.0025) and general dermatologists (AUC, 0.838; P = 0.0038). By integrating close-up and HFUS images, the DMFN model attained an almost identical performance in comparison to dermatologists (AUC, 0.876 vs. AUC, 0.891; P = 0.0080). For the multiclass classification, the DMFN model (AUC, 0.707) exhibited superior prediction performance compared with general dermatologists (AUC, 0.514; P = 0.0043) and dermatologists specialized in HFUS (AUC, 0.640; P = 0.0083), respectively. Compared to dermatologists specialized in HFUS, the DMFN model showed better or comparable performance in diagnosing 9 of the 17 skin diseases. Interpretation: The DMFN model combining analysis of clinical close-up and HFUS images exhibited satisfactory performance in the binary and multiclass classification compared with the dermatologists. It may be a valuable tool for general dermatologists and primary care providers. Funding: This work was supported in part by the National Natural Science Foundation of China and the Clinical research project of Shanghai Skin Disease Hospital.

AbstractObjective To investigate the factors affecting the efficacy of ultrasound (US)-guided percutaneous microwave ablation (PMWA) for adenomyosis with abnormal uterine bleeding (AUB-A).Methods Baseline data of patients with AUB-A who underwent US-guided PMWA treatment between October 2020 and October 2021, including demography characteristics, laboratory and imaging examination results were retrospectively analyzed. 3D reconstruction of magnetic resonance imaging (MRI) was applied to quantitatively assess the local treatment responses, including ratio of non-perfusion volume to adenomyosis volume (NPVr), ablation rate of the endometrial-myometrial junction (EMJ), and surface area (SA) of the ablated part of the EMJ. Patients were followed up at 3, 6, and 12 months after treatment, and divided into two groups: group with complete relief (CR), and group with partial relief (PR) or no relief (NR). Data were compared between them.Results Thirty-one patients were analyzed with a mean age of 38.7 ± 6.8 years (range: 24–48): 48.4% (15/31), 63.3% (19/30), and 65.5% (19/29) achieved CR at 3, 6, and 12 months, respectively. In univariate analysis, compared with the PR/NR group, serum CA125 levels were significantly lower in CR group at 3 months, while ablation rates of EMJ and SA of the ablated part of the EMJ were significantly higher at the three time points. Other baseline characteristics and NPVr did not differ between the two groups.Conclusion Baseline CA125 and ablation rate of the EMJ and SA of the ablated part of the EMJ are associated with the outcome of AUB-A patients after US-guided PMWA treatment.

Abstract Angiogenesis, the formation of new blood vessels, is a complex and dynamic process regulated by various pro- and anti-angiogenic molecules, which plays a crucial role in tumor growth, invasion, and metastasis. With the advances in molecular and cellular biology, various biomolecules such as growth factors, chemokines, and adhesion factors involved in tumor angiogenesis has gradually been elucidated. Targeted therapeutic research based on these molecules has driven anti-angiogenic treatment to become a promising strategy in anti-tumor therapy. The most widely used anti-angiogenic agents include monoclonal antibodies and tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) pathway. However, the clinical benefit of this modality has still been limited due to several defects such as adverse events, acquired drug resistance, tumor recurrence, and lack of validated biomarkers, which impel further research on mechanisms of tumor angiogenesis, the development of multiple drugs and the combination therapy to figure out how to improve the therapeutic efficacy. Here, we broadly summarize various signaling pathways in tumor angiogenesis and discuss the development and current challenges of anti-angiogenic therapy. We also propose several new promising approaches to improve anti-angiogenic efficacy and provide a perspective for the development and research of anti-angiogenic therapy.

Abstract Mitochondria determine the physiological status of most eukaryotes. Mitochondrial dynamics plays an important role in maintaining mitochondrial homeostasis, and the disorder in mitochondrial dynamics could affect cellular energy metabolism leading to tumorigenesis. In recent years, disrupted mitochondrial dynamics has been found to influence the biological behaviors of gastrointestinal cancer with the potential to be a novel target for its individualized therapy. This review systematically introduced the role of mitochondrial dynamics in maintaining mitochondrial homeostasis, and further elaborated the effects of disrupted mitochondrial dynamics on the cellular biological behaviors of gastrointestinal cancer as well as its association with cancer progression. We aim to provide clues for elucidating the etiology and pathogenesis of gastrointestinal cancer from the perspective of mitochondrial homeostasis and disorder.

The purpose of this study was to evaluate the diagnostic performance of multiparametric ultrasound (mpUS; grayscale US, color Doppler US, strain elastography, and contrast-enhanced US) in the assessment of testicular lesions with negative tumoral markers. MpUS imaging data, patient age, serum tumor markers, scrotal pain, cryptorchidism, and related clinical information were retrospectively collected for patients who underwent mpUS examination between January 2013 and December 2019. Histologic results or follow-up examinations were used as the reference standard. In total, 83 lesions from 79 patients were included in the analysis. Fifty-six patients were finally diagnosed with benign tumors, and 23 patients were ultimately diagnosed with malignant tumors. Chi-square tests or Fisher's exact tests were used to assess the difference between the two groups. Stepwise multivariate logistic regression analysis showed that lesion diameter (odds ratio [OR] = 1.072, P = 0.005), vascularization on color Doppler US (OR = 4.066, P = 0.001), and hyperenhancement during the early phase (OR = 6.465, P = 0.047) were significant independent risk factors for malignancy; however, when compared with neoplastic lesions, pain (OR = 0.136, P < 0.001), absence of vascularization on color Doppler US (OR = 1.680, P = 0.042), and nonenhancement during the late phase (OR = 3.461, P = 0.031) were strongly associated with nonneoplastic lesions. MpUS features are useful for differentiating testicular lesions with negative tumoral markers and improving the preoperative diagnosis, which may avoid inappropriate radical orchiectomy.

The purpose of this study was to explore transrectal ultrasound (TRUS) findings of prostate cancer (PCa) guided by multiparametric magnetic resonance imaging (mpMRI) and to improve the Prostate Imaging Reporting and Data System (PI-RADS) system for avoiding unnecessary mpMRI-guided targeted biopsy (TB). From January 2018 to October 2019, fusion mpMRI and TRUS-guided biopsies were performed in 162 consecutive patients. The study included 188 suspicious lesions on mpMRI in 156 patients, all of whom underwent mpMRI-TRUS fusion imaging-guided TB and 12-core transperineal systematic biopsy (SB). Univariate analyses were performed to investigate the relationship between TRUS features and PCa. Then, logistic regression analysis with generalized estimating equations was performed to determine the independent predictors of PCa and obtain the fitted probability of PCa. The detection rates of PCa based on TB alone, SB alone, and combined SB and TB were 55.9% (105 of 188), 52.6% (82 of 156), and 62.8% (98 of 156), respectively. The significant predictors of PCa on TRUS were hypoechogenicity (odds ratio [OR]: 9.595, P = 0.002), taller-than-wide shape (OR: 3.539, P = 0.022), asymmetric vascular structures (OR: 3.728, P = 0.031), close proximity to capsule (OR: 3.473, P = 0.040), and irregular margins (OR: 3.843, P = 0.041). We propose subgrouping PI-RADS score 3 into categories 3a, 3b, 3c, and 3d based on different numbers of TRUS predictors, as the creation of PI-RADS 3a (no suspicious ultrasound features) could avoid 16.7% of mpMRI-guided TBs. Risk stratification of PCa with mpMRI-TRUS fusion imaging-directed ultrasound features could avoid unnecessary mpMRI-TBs.

Purpose Thermal ablation (TA) is a minimally invasive treatment method for symptomatic benign thyroid nodules (BTNs). This study aimed to evaluate the value of TA by comparing the efficacy, safety, and patient satisfaction with conventional/open thyroidectomy (ConT) and endoscopic thyroidectomy (ET) for symptomatic BTNs. Methods Patients with symptomatic BTNs who underwent ConT, ET, or TA therapy between January 2018 and January 2020 were included. Pre-operation data of the two comparisons (TA vs. ConT and TA vs. ET) was balanced using propensity score matching. The technique efficacy (volume reduction ratio ≥50%), nodule disappearance, and regrowth rate were calculated after ablation. The operation and hospitalization time, medical cost, complications, post-operative symptoms, and cosmetic scores were recorded and compared. Patient satisfaction was evaluated using a telephone survey. Results After a median 19-month follow-up (range, 12–36 months), the technique efficacy rate, nodule disappearance, and regrowth rate were 93.2% (119/129), 6.8% (10/129), and 0.8% (1/129), respectively. Operation time, hospitalization time, and medical costs were less for patients in the TA group than for patients in the ConT and ET groups (all p 0.05). Post-operative hypothyroidism was less frequent in the TA group than in the ConT and ET groups (all p

With the full deployment of 5th generation mobile communication network, the optical communication industry has entered the stage of comprehensive and rapid development. According to the demand of data center optical module market, the optical module will develop to high speed and low price in the future. The 400 Gbit/s Quad Small Form Factor Pluggable-Double Density (QSFP-DD) studied in this paper is based on the theory of near Gauss Beam. The optical path is designed and simulated by ZEMAX software, and the spherical parameters are optimized by the optimization function. The coupling efficiency is 74.8%, and the coupling efficiency under different offset is analyzed to get the error range. After analyzing the Fresnel reflection of the contact surface, and comparing the performance of the device under different grinding angles and the high-temperature fiber transmission test of the module, an oblique 8 ° for adaptation is selected. According to the requirements of the protocol, the optical design of this paper with 8 ° angle optical fiber can meet the requirements of the use of the scene.

Abstract Background Triple-negative breast cancer (TNBC) is the most aggressive subtype and occurs in approximately 15–20% of diagnosed breast cancers. TNBC is characterized by its highly metastatic and recurrent features, as well as a lack of specific targets and targeted therapeutics. Epidermal growth factor receptor (EGFR) is highly expressed in a variety of tumors, especially in TNBC. LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory. This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action. Methods LR004-VC-MMAE was prepared by coupling a cytotoxic payload (MMAE) to an anti-EGFR antibody (LR004) via a linker, and the drug-to-antibody ratio (DAR) was analyzed by HIC-HPLC. The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset (GSE41313) and Western blotting. MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE (0, 0.0066, 0.066, 0.66, 6.6 nmol/L), and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation. The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VC-MMAE concentrations (2.5 and 5 nmol/L) with wound healing and Transwell invasion assays. Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells in MDA-MB-468 and MDA-MB-231 cells. The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo. Briefly, BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDA-MB-231 cells. Then they were randomly divided into 4 groups (n = 6 per group) and treated with PBS, naked LR004 (10 mg/kg), LR004-VC-MMAE (10 mg/kg), or doxorubicin, respectively. Tumor sizes and the body weights of mice were measured every 4 days. The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR, ERK, MEK phosphorylation and tumor stemness marker gene expression. Results LR004-VC-MMAE with a DAR of 4.02 were obtained. The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells (P

Background: Rural general practitioners (GPs) have insufficient diagnostic information to deal with complex clinical scenarios due to the inequality in medical imaging resources in rural and remote communities. The objective of this study is to explore the value of a tele-mentored handheld ultrasound (tele-HHUS) system, allowing GPs to provide ultrasound (US) services in rural and remote communities. Methods: Overall, 708 patients underwent tele-HHUS examination between March and October 2021 and March and April 2022 across thirteen primary hospitals and two tertiary-care general hospitals. All US examinations were guided and supervised remotely in real time by US experts more than 300 km away using the tele-HHUS system. The following details were recorded: location of tele-HHUS scanning, primary complaints, clinical diagnosis, and US findings. The recommendations (referral or follow-up) based on clinical experience alone were compared with those based on clinical experience with tele-HHUS information. Results: Tele-HHUS examinations were performed both in hospital settings (90.6%, 642/708) and out of hospital settings (9.4%, 66/708). Leaving aside routine physical examinations, flank pain (14.2%, 91/642) was the most common complaint in inpatients, while chest distress (12.1%, 8/66) and flank discomfort (12.1%, 8/66) were the most common complaints in out-of-hospital settings. Additionally, the referral rate increased from 5.9% to 8.3% (kappa = 0.202; p = 0.000). Conclusions: The tele-HHUS system can help rural GPs perform HHUS successfully in remote and rural communities. This novel mobile telemedicine model is valuable in resource-limited areas.

With the demand of data center traffic soaring, many service providers are already working on 400 Gbit/s Ethernet communication systems. Compared with the 100 Gbit/s optical module, the 400 Gbit/s optical module can provide higher transmission bandwidth with lower power consumption and cost. Aiming at the above requirements, this paper proposes a design scheme of 400 Gbit/s optical transceiver module for data center optical communication network system. We first introduce the 400 Gbit/s optical module related protocols and standards. Then we present the general design of the module framework, mainly from the rate of conversion, launch, receive and monitoring 4 parts. Finally, we conduct a performance test and the test results show that the module in accordance with the agreement and the provisions of the standard, which is a good solution to realize data center 400 Gbit/s Ethernet transmission.

Abstract Background The effects of dietary factors on prognosis of esophageal cancer remain unclear. This systematic review and meta-analysis aimed to assess the association between dietary intake and the risk of mortality among patients with esophageal cancer. Methods Six electronic databases (PubMed, Web of Science, OVID, ProQuest, CNKI and Wanfang) were searched for studies published up to Oct. 2019 that examined the association between dietary intake and all-cause mortality, esophageal cancer-specific mortality and esophageal cancer recurrence. The pooled hazard ratio (HR) with 95% confidence interval (CI) were derived by comparing the highest with the lowest categories of each dietary item and by using random effect models. Results A total of 15 cohort studies were included in this study and all reported pre-diagnosis dietary exposure; two focused on dietary folate, 12 on alcohol consumption and three on other dietary components (sugary beverages, phytochemicals and preserved vegetables). When comparing the highest with the lowest categories, dietary folate intake was associated with a reduced risk of esophageal cancer-specific mortality in patients with esophageal squamous cell carcinoma (HR: 0.41, 95% CI: 0.25–0.69), with low heterogeneity (I 2 = 0%, P = 0.788). When comparing the highest with the lowest categories of alcohol consumption, alcohol consumption was associated with an increased risk of all-cause mortality in patients with esophageal squamous cell carcinoma (HR: 1.29, 95% CI: 1.07–1.55; heterogeneity: I 2 = 53%, P = 0.030), but this increased risk was not significant in patients with esophageal adenocarcinoma (HR = 1.05, 95% CI: 0.84–1.32). Conclusions This review with pre-diagnostic dietary exposure showed that dietary folate intake was associated with a reduced risk of mortality of esophageal squamous cell carcinoma, whereas alcohol consumption was associated with an increased risk. More studies are needed to investigate effect of dietary factors, especially post-diagnosis dietary consumption, on esophageal cancer prognosis.

Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity with a conspicuous tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma (GC) cells. In accordance with these observations, overexpression of CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, while knockdown of CXCL8 with siRNA inhibited cell proliferation and migration of AGS-EBV cells. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitors BAY 11-7082 and BMS345541. Furthermore, EBV-encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 overexpression. Finally, CXCL8 is positively correlated with overall survival in GC patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in GC via NF-κB signaling, and CXCL8 might serve as a novel anti-tumor target for EBVaGC.

Background: Preoperative determination of breast cancer molecular subtypes facilitates individualized treatment plan-making and improves patient prognosis. We aimed to develop an assembled convolutional neural network (ACNN) model for the preoperative prediction of molecular subtypes using multimodal ultrasound (US) images. Methods: This multicentre study prospectively evaluated a dataset of greyscale US, colour Doppler flow imaging (CDFI), and shear-wave elastography (SWE) images in 807 patients with 818 breast cancers from November 2016 to February 2021. The St. Gallen molecular subtypes of breast cancer were confirmed by postoperative immunohistochemical examination. The monomodal ACNN model based on greyscale US images, the dual-modal ACNN model based on greyscale US and CDFI images, and the multimodal ACNN model based on greyscale US and CDFI as well as SWE images were constructed in the training cohort. The performances of three ACNN models in predicting four- and five-classification molecular subtypes and identifying triple negative from non-triple negative subtypes were assessed and compared. The performance of the multimodal ACNN was also compared with preoperative core needle biopsy (CNB). Finding: The performance of the multimodal ACNN model (macroaverage area under the curve [AUC]: 0.89–0.96) was superior to that of the dual-modal ACNN model (macroaverage AUC: 0.81–0.84) and the monomodal ACNN model (macroaverage AUC: 0.73–0.75) in predicting four-classification breast cancer molecular subtypes, which was also better than that of preoperative CNB (AUC: 0.89–0.99 vs. 0.67–0.82, p

Objective: Ultrasound (US) plays an important role in the diagnosis and management of breast diseases; however, effective breast US screening is lacking in rural and remote areas. To alleviate this issue, we prospectively evaluated the clinical availability of 5G-based telerobotic US technology for breast examinations in rural and remote areas. Methods: Between September 2020 and March 2021, 63 patients underwent conventional and telerobotic US examinations in a rural island (Scenario A), while 20 patients underwent telerobotic US examination in a mobile car located in a remote county (Scenario B) in May 2021. The safety, duration, US image quality, consistency, and acceptability of the 5G-based telerobotic US were assessed. Results: In Scenario A, the average duration of the telerobotic US procedure was longer than that of conventional US (10.3 ± 3.3 min vs. 7.6 ± 3.0 min, p = 0.017), but their average imaging scores were similar (4.86 vs. 4.90, p = 0.159). Two cases of gynecomastia, one of lactation mastitis, and one of postoperative breast effusion were diagnosed and 32 nodules were detected using the two US methods. There was good interobserver agreement between the US features and BI-RADS categories of the identical nodules (ICC = 0.795–1.000). In Scenario B, breast nodules were detected in 65% of the patients using telerobotic US. Its average duration was 10.1 ± 2.3 min, and the average imaging score was 4.85. Overall, 90.4% of the patients were willing to choose telerobotic US in the future, and tele-sonologists were satisfied with 85.5% of the examinations. Conclusion: The 5G-based telerobotic US system is feasible for providing effective breast examinations in rural and remote areas.

Abstract Background The accurate evaluation of BRAFV600E mutation in preoperative fine‐needle aspiration cytology (FNAC) specimens is important for making management decisions in thyroid nodules (TNs). The aim of this study was to assess the false‐positive and false‐negative BRAFV600E mutations in thyroid FNAC specimens and their influence on diagnosis of TN. Methods This prospective study enrolled 292 nodules in 269 patients who underwent BRAFV600E mutation analysis using amplification refractory mutation system‐quantitative real‐time polymerase chain reaction (ARMS‐qPCR) both in FNAC specimens and formalin‐fixed, paraffin‐embedded (FFPE) tissue samples after surgery. The false‐positive and false‐negative mutations for BRAFV600E analysis using ARMS‐qPCR in FNAC specimens were recorded, with reference to the results of BRAFV600E mutation analysis using ARMS‐qPCR in FFPE tissue sample. Diagnostic performances of FNAC, BRAFV600E mutation analysis in FNAC specimens, BRAFV600E mutation analysis in FFPE tissue sample, and the combination of FNAC and BRAFV600E mutation analysis for predicting thyroid malignancy were assessed. Results The false‐positive and false‐negative mutations for BRAFV600E analysis using ARMS‐qPCR in FNAC specimens were 10.1% (19/189) and 7.1% (7/98), respectively. FNAC combined with preoperative BRAFV600E mutation analysis significantly increased the diagnostic sensitivity from 75.7% to 92.3%, and accuracy from 78.7% to 90.6% in comparison with FNAC alone (both P .05). Conclusions FNAC combined with preoperative BRAFV600E mutation analysis can significantly increase the diagnostic performance in comparison with FNAC alone. False‐positive and false‐negative BRAFV600E mutation results are found in preoperative FNAC specimens, whereas it does not affect the overall auxiliary diagnosis of TNs.

Due to the increasing rates of physical examination and application of advanced ultrasound machines, incidences of benign thyroid nodules (BTNs) and papillary thyroid microcarcinoma (PTMC) were dramatically up-regulated in recent years. Thermal ablation (TA) has been widely used and regarded as a safe and effective method to eliminate or reduce BTNs and recurrent low-risk PTMC. However, conclusions using TA to treat primary PTMC are controversial. Recently, several long-term and prospective studies on TA treatment of BTNs and primary PTMC have been reported. Here, we review current literatures and progress on TA treatment of BTNs and PTMC and underline the way to get the best treatment outcomes, providing a comprehensive insight into the research progresses in this field.

Objective: TNFAIP2 is a novel gene induced by TNF-α and participates in inflammatory reaction and tumor angiogenesis. This study aims to understand the correlation between TNFAIP2 gene polymorphism and prediction as well as prognosis of gastric cancer (GC) in a Chinese population.Methods: One thousand two hundred seventy-nine cases were enrolled, including 640 GC and 639 non-cancer cases. The functional tagSNPs of the TNFAIP2 gene were screened by Haploview software and NIH Snpinfo website. Human whole-blood genomic DNA was extracted by phenol chloroform method and analyzed by KASP SNP typing and sequencing method. ELISA was used to determine the expression of TNFAIP2 protein in serum samples. The miRNAs bound to TNFAIP2 3′ UTR rs8126 were predicted by MirSNP and TargetScan database. SPSS 22.0 software was used for statistical analysis, and P < 0.05 showed statistical difference.Results: Four functional TNFAIP2 tagSNPs were found by bioinformatics analysis. TNFAIP2 rs8126 T>C polymorphism increased GC risk, and the risk in TC genotype cases was higher than that in TT genotype cases (P = 0.001, OR = 1.557). In the dominant model, the TNFAIP2 rs8126 polymorphic carrier was 1.419 times higher (P = 0.007). TNFAIP2 rs710100 C>T polymorphism, TNFAIP2 rs3759571 G>A polymorphism, and TNFAIP2 rs3759573 A>G polymorphism were not correlated with GC risk. In the subgroup analysis, TNFAIP2 rs8126 TC genotype cases had a higher GC risk in male, aged 60 years or older, Helicobacter pylori-negative, non-smoking, and non-drinking. However, there was no correlation between TNFAIP2 SNPs and GC prognosis. The TNFAIP2 protein concentration in GC patients was significantly different from that in healthy persons (P = 0.029), but it was not associated with GC prognosis. The high or low expression of TNFAIP2 protein had no significant difference with gender, age, H. pylori infection, smoking, and drinking in GC patients. The serum TNFAIP2 protein expression in rs8126 TT genotype carriers was significantly higher than that in rs8126 CC genotype carriers (P < 0.001).Conclusion: TNFAIP2 3′ UTR rs8126 T>C polymorphism was associated with GC risk in a Chinese population, especially in cases with males aged 60 years or older, H. pylori negative, non-smoking and non-drinking. Compared with healthy persons, serum TNFAIP2 protein expression was higher in Chinese GC patients, and TNFAIP2 3′ UTR rs8126 T>C polymorphism might affect TNFAIP2 protein expression.

Abstract Background Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. However, there is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD. Methods Serum levels of MMP9 and TLR4 were measured by enzyme-linked immunosorbent assay (ELISA) in 88 AAD patients and 88 controls. The clinical test related information was collected from patients’ electronic medical records. Results Serum MMP9 and TLR4 levels were significantly higher in AAD patients than those in healthy controls in the general and stratified comparisons. Either serum MMP9 or TLR4 was independently associated with the risk of AAD (all p

Abstract Background The molecular mechanism of Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) remains elusive. A collection of molecular regulators including transcription factor and noncoding RNA (ncRNAs) may affect the carcinogenesis of EBVaGC by regulating the expression and function of key genes. In this study, integration of multi-level expression data and bioinformatics approach was used to identify key elements and their interactions involved in mechanism of EBVaGC and their network regulation. Methods Data of the gene expression profiling data sets (GSE51575) was downloaded from GEO database. Differentially expressed genes between EBVaGC and normal samples were identified by GEO2R. Gene ontology and pathway enrichment analyses were performed using R packages Cluster profiler. STRING database was used to find interacting proteins between different genes. Transcription factors in differentially expressed genes were obtained from TF Checkpoint database. Using Cytoscape, we built transcription factor regulation network. miRNAs involved in the gene-interacting proteins and the miRNA-targeted lncRNA were predicted through miRWalk. Using ViRBase, EBV related miRNA regulation network was built. Overlapping genes and regulators of the above three networks were further identified, and the cross network was constructed using Cytoscape software. Moreover, the differential expressions of the target genes and transcription factors in the cross network were explored in different molecular subtypes of GC using cBioPortal. By histological verification, the expression of two main target genes in the cross network were further analyzed. Results A total of 104 genes showed differential expressions between EBVaGC and normal tissues, which were associated with digestion, G-protein coupled receptor binding, gastric acid secretion, etc. Pathway analysis showed that the differentially expressed genes were mainly enriched in gastric acid secretion and protein digestion and absorption. Using STRING dataset, a total of 54 proteins interacted with each other. Based on the transcription factor network, the hub transcription factors IRX3, NKX6-2, PTGER3 and SMAD5 were identified to regulate their target genes SST and GDF5, etc. After screening and matching in miRwalk datasets, a ceRNA network was established, in which the top five miRNAs were hsa-miR-4446-3p, hsa-miR-5787, hsa-miR-1915-3p, hsa-miR-335-3p and hsa-miR-6877-3p, and the top two lncRNAs were RP5-1039K5.19 and TP73-AS1. According to the EBV related miRNA regulation network, CXCL10 and SMAD5 were found to be regulated by EBV-miR-BART1-3p and EBV-mir-BART22, respectively. By overlapping the three networks, CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22 were found to be key elements of regulation mechanism of EBVaGC. CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. Conclusion In the current study, our results revealed key elements and their interactions involved in EBVaGC. Some hub transcription factors, miRNAs, lncRNAs and EBV related miRNAs were observed to regulate their target genes. Overlapping genes and regulators were observed in diverse regulation networks, such as CXCL10, GDF5, PTGER3, SMAD5, miR-6877-3p, RP5-1039K5.19, TP73-AS1, EBV-miR-BART1-3p and EBV-mir-BART22. Moreover, CXCL10, GDF5, PTGER3 and SMAD5 were also differentially expressed among the four molecular subtypes of GC. The histological verification experiment showed differential expressions of the two main target genes GDF5 and CXCL10 between EBVaGC and non-tumor tissues as well as EBVnGC. Therefore, the identified key elements and their network regulation may be specifically involved in EBVaGC mechanisms.

Abstract To investigate the diagnostic performance of combination of ultrasound (US) thyroid imaging reporting and data system (TI-RADS) and a new US scoring system for diagnosing thyroid nodules (TNs) with indeterminate results (Bethesda categories III, IV and V) on fine-needle aspiration (FNA) cytology. 453 patients with 453 cytologically indeterminate TNs were included in this study. Multivariate analyses were performed to construct the scoring system. The diagnostic performances of TI-RADS and the combined method were evaluated and compared. Multivariate analyses revealed that marked hypoechogenicity, taller than wide shape and absence of halo sign were independent predictors for malignancy in cytologically indeterminate TNs. Scoring system was thereafter defined as follows: risk score (RS) = 3.2 x (if marked hypoechogenicity) + 2.8 x (if taller than wide shape) + 1.3 x (if absence of halo sign). Compared with TI-RADS alone, the areas under the receiver operating characteristic curves (AUC), specificity, accuracy and positive predictive value (PPV) of the combined method increased significantly with 0.731 versus 0.569, 48.5% versus 14.1%, 76.2% versus 62.3%, and 70.9% versus 59.9%, respectively (all P

Abstract To develop a risk model for predicting axillary lymph node metastasis (LNM) in patients with breast invasive ductal carcinoma (IDCs) using ultrasound (US), US elastography of virtual touch tissue imaging (VTI) and virtual touch tissue imaging & quantification (VTIQ), and histologic parameters. This study included 162 breast IDCs in 162 patients. Univariate and multivariate analyses were used to identify the risk factors and a risk model was created. The results found that 64 (39.5%) of 162 patients had axillary LNMs. The risk score (RS) for axillary LNM was defined as following: RS = 1.3 × (if lesion size ≥20 mm) + 2.6 × (if taller than wide shape) + 2.2 × (if VTI score ≥5) + 3.9 × (if histological grade III) + 1.9 × (if positive C-erbB-2). The rating system was divided into 6 stages (i.e. Stage I, Stage II, Stage III, Stage IV, Stage V, and Stage VI) and the associated risk rates in terms of axillary LNM were 0% (0/19), 6.1% (2/33), 7.7% (3/39), 65.5% (19/29), 92.3% (24/26), and 100% (16/16), respectively. The risk model for axillary LNM established in the study may facilitate subsequent treatment planning and management in patients with breast IDCs.

Purpose Ethics review processes have become increasingly complex. The objective of this study was to explore the challenges currently faced in ethics reviews of clinical scientific research projects in China, with the goal of standardizing the structure of medical ethics committees and better protecting the rights and interests of research participants. Methods We reviewed and comprehensively analyzed the available literature discussing standardized ethics reviews of clinical scientific research projects. Results We identified the following problems: incomplete legislation, absence of supervision, vague review criteria, limitations of ethics committee competence, inadequate ethics consciousness, and poor tracking of reviews. In this paper, we suggest strategies for the development of future ethical reviews of clinical scientific research projects. Conclusion To standardize the ethics review process of clinical scientific research projects in China, it is necessary to establish relevant laws and regulations and implement supervisory responsibilities. Professional training of medical ethics committees is suggested as an effective way to improve the quality of ethics reviews.

Background: Bee propolis, a mixture of the secretion from bee tongue gland and wax gland, was collected from the tree bud and barked by bees. The components were rich in terpenes, phenolics, and flavonoids, and had anti-cancer, anti-bacterial, anti-inflammatory, hepatoprotective, and neuroprotection abilities. However, the potential anti-oxidative stress of propolis was not well documented. This study aimed to study the protective effect of propolis on high-incident nonfatal diseases, such as stroke and cerebral infarction caused by ischemia. Objective: Oxidative stress caused by acute stroke results in inflammation and injury followed by cell damage and apoptosis. Clarification of the anti-oxidative stress effect of propolis may contribute to stroke prevention and damage reduction. Design: Propolis was separated and purified into 70% ethanol and dichloromethane extracts systematically. The fraction three (Fr.3) of dichloromethane was further separated into pinocembrin, pinobanksin, pinobanksin-3-acetate, chrysin, and galangin by chromatography. Compounds extracted from propolis were tested for cell-protection effects in an oxygen-glucose deprivation (OGD) N2a cell model. MTT assay, oxidative stress markers measurement, flow cytometry, and QPCR were used to evaluate cell viability and apoptosis. Results: All compounds, especially pinocembrin and galangin, enhanced cell viability in OGD-treated N2a cells. In addition, anti-oxidative enzymes were elevated and cellular Ca2+ was reduced. They also had extreme anti-apoptosis effects by up-regulating the expression of Bcl-2 mRNA and down-regulating caspase-3 and Bax expression. Taken together, propolis had anti-oxidative effects on stress and protected cells from damage. Conclusion: The anti-oxidative effect of propolis can be applied to daily food supplements and may benefit stroke patients.

Safflower honey is a unique type of monofloral honey collected from the nectar of Carthamus tinctorius L. in the Apis mellifera colonies of northwestern China. Scant information is available regarding its chemical composition and biological activities. Here, for the first time, we investigated this honey’s chemical composition and evaluated its in vitro antioxidant and anti-inflammatory activities. Basic physicochemical parameters of the safflower honey samples in comparison to established quality standards suggested that safflower honeys presented a good level of quality. The in vitro antioxidant tests showed that extract from Carthamus tinctorius L. honey (ECH) effectively scavenged DPPH and ABTS+ free radicals. In lipopolysaccharides (LPS) activated murine macrophages inflammatory model, ECH treatment to the cells inhibited the release of nitric oxide and down-regulated the expressions of inflammatory-relating genes (iNOS, IL-1β, TNF-α and MCP-1). The expressions of the antioxidant genes TXNRD, HO-1, and NQO-1, were significantly boosted in a concentration-dependent manner. ECH decreased the phosphorylation of IκBα and inhibited the nuclear entry of the NF-κB-p65 protein, in LPS-stimulated Raw 264.7 cells, accompany with the increased expressions of Nrf-2 and HO-1, suggesting that ECH achieved the anti-inflammatory effects by inhibiting NF-κB signal transduction and boosting the antioxidant system via activating Nrf-2/HO-1 signaling. These results, taken together, indicated that safflower honey has great potential into developing as a high-quality agriproduct.

Objective To investigate the association between polymorphisms of the interleukin 10 ( IL10 ) gene and risk of gastric cancer (GC) and atrophic gastritis (AG). Methods This study enrolled patients with GC, patients with AG and healthy control subjects. Demographic data were collected and the IL10 gene –1082A/G, –819C/T and –592A/C polymorphisms were genotyped. An enzyme-linked immunosorbent assay was performed to detect Helicobacter pylori infection. Results The study enrolled 556 participants including 208 in the GC group, 116 in the AG group and 232 controls (CON group). In a recessive model of the IL10 –819C/T polymorphism, a significantly decreased risk of GC was found compared with AG and non-cancer subjects, respectively (AG→GC: odds ratio OR 0.41; non-cancer→GC: OR 0.57). The CC genotype demonstrated a significantly increased risk of AG compared with CON. Similar significant results were detected in males and H. pylori -negative subgroups. The ACC haplotype was associated with a decreased risk of GC compared with AG. The ATC haplotype was associated with a decreased risk of AG compared with the CON group, but it was associated with an increased risk of GC compared with AG. Conclusion The IL10 gene promoter –819C/T (rs1800871) polymorphism was associated with the risk of GC and AG in a Chinese population.

Glucagon and insulin have opposing action in governing glucose homeostasis. In type 2 diabetes mellitus (T2DM), plasma glucagon is characteristically elevated, contributing to increased gluconeogenesis and hyperglycemia. Therefore, glucagon receptor (GCGR) antagonism has been proposed as a pharmacologic approach to treat T2DM. In support of this concept, a potent small-molecule GCGR antagonist (GRA), MK-0893, demonstrated dose-dependent efficacy to reduce hyperglycemia, with an HbA1c reduction of 1.5% at the 80 mg dose for 12 weeks in T2DM. However, GRA treatment was associated with dose-dependent elevation of plasma LDL-cholesterol (LDL-c). The current studies investigated the cause for increased LDL-c. We report findings that link MK-0893 with increased glucagon-like peptide 2 and cholesterol absorption. There was not, however, a GRA-related modulation of cholesterol synthesis. These findings were replicated using structurally diverse GRAs. To examine potential pharmacologic mitigation, coadministration of ezetimibe (a potent inhibitor of cholesterol absorption) in mice abrogated the GRA-associated increase of LDL-c. Although the molecular mechanism is unknown, our results provide a novel finding by which glucagon and, hence, GCGR antagonism govern cholesterol metabolism.

Angiogenesis is a crucial requirement for malignant tumor growth, progression and metastasis. Tumor-derived factors stimulate formation of new blood vessels which actively support tumor growth and spread. Various of drugs have been applied to inhibit tumor angiogenesis. CPU-12, 4-chloro-N-(4-((2-(4-methoxyphenyl)-5-methyloxazolo[5,4-d] pyrimidin-7-yl)amino)phenyl)benzamide, is a novel oxazolo[5,4-d]pyrimidine derivative that showed potent activity in inhibiting VEGF-induced angiogenesis in vitro and ex-vivo. In cell toxicity experiments, CPU-12 significantly inhibited the human umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner with a low IC50 value at 9.30 ± 1.24 μM. In vitro, CPU-12 remarkably inhibited HUVEC's migration, chemotactic invasion and capillary-like tube formation in a dose-dependent manner. In ex-vivo, CPU-12 effectively inhibited new microvessels sprouting from the rat aortic ring. In addition, the downstream signalings of vascular endothelial growth factor receptor-2 (VEGFR-2), including the phosphorylation of PI3K, ERK1/2 and p38 MAPK, were effectively down-regulated by CPU-12. These evidences suggested that angiogenic response via the induction of VEGFR through distinct signal transduction pathways regulating proliferation, migration and tube formation of endothelial cells was significantly inhibited by the novel small molecule compound CPU-12 in vitro and ex-vivo. In conclusion, CPU-12 showed superior anti-angiogenic activity in vitro.

Jellyfish gelatin was hydrolyzed by different proteases to obtain antioxidative polypeptides. The gelatin hydrolysate obtained by progressive hydrolysis using trypsin and Properase E exhibited the highest hydrolysis degree and antioxidant activity. Three series of gelatin polypeptides (SCP1, SCP2 and SCP3) were obtained by ultrafiltrating the gelatin hydrolysate through molecular mass cut-off membranes of 10, 6 and 2 kDa, respectively. Amino acid composition analysis showed that SCP3 had the highest total hydrophobic amino acid content. The in vitro antioxidant tests demonstrated that SCP2 had the strongest hydroxyl radical and hydrogen peroxide scavenging activities and metal chelating ability, while SCP3 showed the highest reducing power, antioxidant activity in linoleic acid emulsion system and superoxide anion radical scavenging activity. The results support the feasibility of jellyfish gelatin as a natural antioxidant polypeptide provider, and enzymatic hydrolysis and ultrafiltration could be potent future processing technologies to utilize the abundant jellyfish resource.

Chinese propolis (CP), an important hive product, can alleviate inflammatory responses. However, little is known regarding the potential of propolis treatment for mastitis control. To investigate the anti-inflammatory effects of CP on bovine mammary epithelial cells (MAC-T), we used a range of pathogens to induce cellular inflammatory damage. Cell viability was determined and expressions of inflammatory/antioxidant genes were measured. Using a cell-based reporter assay system, we evaluated CP and its primary constituents on the NF-κB and Nrf2-ARE transcription activation. MAC-T cells treated with bacterial endotoxin (lipopolysaccharide, LPS), heat-inactivated Escherichia coli, and Staphylococcus aureus exhibited significant decreases in cell viability while TNF-α and lipoteichoic acid (LTA) did not. Pretreatment with CP prevented losses in cell viability associated with the addition of killed bacteria or bacterial endotoxins. There were also corresponding decreases in expressions of proinflammatory IL-6 and TNF-α mRNA. Compared with the mastitis challenged cells, enhanced expressions of antioxidant genes HO-1, Txnrd-1, and GCLM were observed in CP-treated cells. CP and its polyphenolic active components (primarily caffeic acid phenethyl ester and quercetin) had strong inhibitive effects against NF-κB activation and increased the transcriptional activity of Nrf2-ARE. These findings suggest that propolis may be valuable in the control of bovine mastitis.

BACKGROUND: Xeroderma pigmentosum group G (XPG) plays a critical role in preventing cells from oxidative DNA damage. This study aimed to investigate XPG protein expression in different gastric tissues and in patients with diverse prognoses, thus providing insights into its role in the development, progression and prognosis of gastric cancer (GC). METHODS: A total of 176 GC, 131 adjacent non-tumour tissues, 53 atrophic gastritis (AG) and 49 superficial gastritis (SG) samples were included. Immunohistochemical staining was used to detect XPG protein expression. RESULTS: XPG expression was significantly higher in GC tissues compared with adjacent non-tumour tissues. In the progressive disease sequence SG→AG→GC, XPG expression was significantly higher in AG and GC compared with SG. Analysis of clinicopathological parameters and survival in GC patients demonstrated a significant association between XPG expression level and depth of tumour invasion, macroscopic type, Lauren's classification, smoking, Helicobacter pylori infection and family history. Cox multivariate survival analysis indicated that patients with positive XPG expression had significantly longer overall survival (P = 0.020, HR = 0.394, 95%CI 0.179-0.866), especially in aged younger than 60 years (P = 0.027, HR = 0.361, 95%CI 0.147-0.888) and male patients (P = 0.002, HR = 0.209, 95%CI 0.077-0.571). CONCLUSIONS: This study demonstrated that XPG protein expression was related to the development, progression and prognosis of GC, and might thus serve as a potential biomarker for its diagnosis and prognosis.

BACKGROUND: The aim of this study was to investigate the interaction effects of pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross complementing group 6 (ERCC6) gene polymorphisms and its association with the risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA polymorphism or a combination of several polymorphisms that could serve as biomarkers for predicting the risk of gastric cancer and its precancerous diseases. METHODS: Sequenom MassARRAY platform method was used to detect polymorphisms of pri-let-7a-1 rs10739971 G → A, PGC rs4711690 C → G, PGC rs6458238 G → A, PGC rs9471643 G → C, and ERCC6 rs1917799 in 471 gastric cancer patients, 645 atrophic gastritis patients and 717 controls. RESULTS: An interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799 polymorphism was observed for the risk of gastric cancer (P interaction = 0.026); and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC rs6458238 polymorphism (P interaction = 0.012) and PGC rs9471643 polymorphism (P interaction = 0.039) were observed for the risk of atrophic gastritis. CONCLUSION: The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and PGC polymorphisms could provide a greater prediction potential than a single polymorphism on its own. Large-scale studies and molecular mechanism research are needed to confirm our findings.

BACKGROUND: Pepsinogen C (PGC) plays an important role in sustaining the cellular differentiation during the process of gastric carcinogenesis. This study aimed to assess the role of PGC tagSNPs and their interactions with Helicobacter pylori (H. pylori) in the development of gastric cancer and its precursor, atrophic gastritis. METHODS: Four PGC tagSNPs (rs6941539, rs6912200, rs3789210 and rs6939861) were genotyped by Sequenom MassARRAY platform in a total of 2311 subjects consisting of 642 gastric cancer, 774 atrophic gastritis, and 895 healthy control subjects. The mRNA and protein expression levels of PGC in gastric tissues and in serum were respectively measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), immunohistochemistry, and Eenzyme-linked immunoabsorbent assay (ELISA). RESULTS: We found associations between PGC rs3789210 CG/GG genotypes and reduced gastric cancer risk and between PGC rs6939861 A variant allele and increased risks of both gastric cancer and atrophic gastritis. As for the haplotypes of PGC rs6941539-rs6912200-rs3789210-rs6939861 loci, the TTCA and TTGG haplotypes were respectively associated with increased and reduced risks of both gastric cancer and atrophic gastritis; additionally, the CTCA haplotype was associated with increased atrophic gastritis risk. Very interestingly, rs6912200 CT/TT genotypes had a positive interaction with H. pylori, synergistically elevating the gastric cancer risk. Moreover, healthy subjects who carried rs6912200 CT, TT and CT/TT variant genotypes had lower histological and serum expression levels of PGC protein. CONCLUSIONS: Our findings highlight an important role of PGC rs3789210 and rs6939861 in altering susceptibility to atrophic gastritis and/or gastric cancer. Moreover, people who carry rs6912200 variant genotypes exhibit higher gastric cancer risk in case of getting H. pylori infection, which strongly suggest a necessity of preventing and/or eliminating H. pylori infection in those individuals.

Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinese population. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790-6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475-5.521; OR = 1.638; 95% CI = 1.044-2.571; OR = 1.641; 95% CI = 0.983-2.739, respectively) (p