An Update of G-Protein-Coupled Receptor Signaling and Its Deregulation in Gastric Carcinogenesis.

G-protein-coupled receptors (GPCRs) belong to a cell surface receptor superfamily responding to a wide range of external signals. The binding of extracellular ligands to GPCRs activates a heterotrimeric G protein and triggers the production of numerous secondary messengers, which transduce the extracellular signals into cellular responses. GPCR signaling is crucial and imperative for maintaining normal tissue homeostasis. High-throughput sequencing analyses revealed the occurrence of the genetic aberrations of GPCRs and G proteins in multiple malignancies. The altered GPCRs/G proteins serve as valuable biomarkers for early diagnosis, prognostic prediction, and pharmacological targets. Furthermore, the dysregulation of GPCR signaling contributes to tumor initiation and development. In this review, we have summarized the research progress of GPCRs and highlighted their mechanisms in gastric cancer (GC). The aberrant activation of GPCRs promotes GC cell proliferation and metastasis, remodels the tumor microenvironment, and boosts immune escape. Through deep investigation, novel therapeutic strategies for targeting GPCR activation have been developed, and the final aim is to eliminate GPCR-driven gastric carcinogenesis.

Highly Sensitive Lanthanide-Doped Nanoparticles-Based Point-of-Care Diagnosis of Human Cardiac Troponin I.

INTRODUCTION: Cardiac troponin I (cTnI) has been regarded as a gold standard for early diagnosis and prognosis monitoring of acute myocardial infarction (AMI) in clinical practice. Owing to its low concentration in blood, accurate determination of cTnI often requires high sensitivity. However, current established point-of-care (POC) assays are insufficient to meet clinically analytical requirements due to their low sensitivity. METHODS: To this end, we established a highly sensitive and reliable POC lateral flow strip based on lanthanide-doped nanoparticles (NPs) for cTnI determination in human blood samples. The capture of cTnI on the lateral flow strip was performed in a sandwich assay, where Eu3+-doped vanadate nanoparticles (GdVO4:30% Eu NPs) were used as luminescent probes to allow quantification. RESULTS: Our platform realized the analytical sensitivity enhancement with limit-of-detection (LOD) as low as 17 pg mL-1 for cTnI detection, which was lower than the commercial counterpart; meanwhile, it displayed high specificity, excellent reproducibility and outstanding accuracy for analyzing clinical serum samples. CONCLUSION: Overall, this strategy provided an ultrasensitive, cost-effective and user-friendly platform for on-site cTnI detection, demonstrating the prospect of lanthanide-doped NPs-based POC diagnosis of disease-related biomarkers.

[Efficacy and Safety of Decitabine Combined with CAG (Cytarabine, Aclarubicin, G-CSF) for Patients with Intermediate or High Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia: a Meta-Analysis].

OBJECTIVE: To systematically evaluate the efficacy and safety of DCAG regimen for treating the intermediate or high risk MDS and AML. METHODS: PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials (RCTs) of decitabine combined with CAG regimen for intermediate or high risk MDS and AML from inception to March, 2018. The quality of each RCT was evaluated by the Cochrane collaboration´s tool for assessing the risk of bias.Then, the data were analyzed by using RevMan 5.3. RESULTS: Twenty-four RCTs were included in the meta-analysis, containing 1 557 patients with intermediate or high-risk MDS and AML, of whom 594 were AML patients and 590 were MDS patients. The patients treated with the DCAG regimen were enrolled in DCAG group, and the patients treated with single-agent decitabine or CAG regimen were enrolled in control group. RESULTS: The results of meta-analysis showed that compared with other therapies, the complete remission rate of DCAG regimen in patients with intermediate or high-risk MDS and AML was high (RR=1.63，95% CI=1.43-1.85，P＜0.000 01), and the overall response rate was also high (RR=1. 35，95% CI=1.24-1.46，P＜0.000 01); Subgroup analysis results showed that DCAG regimen was better than CAG regimen in the complete remission rate (RR=1.71，95% CI=1.49-1.97，P＜0.000 01), and slightly better than single-agent decitabine group (RR=1.43，95% CI=1.08-1.91，P=0.01). In terms of adverse reactions, there was no statistically significant difference in the rates of myelosuppression, pulmonary infection, gastrointestinal reactions, and bleeding events between the 2 groups (P＞0.05). CONCLUSION: DCAG regimen has significant efficacy in the treatment of intermediate or high-risk MDS and AML, and is superior to CAG regimen and single-agent dicitabine regimen. As compared with control group, there was no significant difference in adverse events. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above mentioned conclusion.

[Interferon-induced transmembrane protein 3 knock-down inhibits proliferation and invasion of hepatocellular carcinoma HepG2 cells in vitro].

OBJECTIVE: To investigate the abnormal expression of interferon-induced transmembrane protein 3 (IFITM3) in hepatocellular carcinoma (HCC) and the effect of IFITM3 knock-down on the biological behaviors of hepatocellular carcinoma HepG2 cells. METHODS: Western blot analysis and immunohistochemical staining were used to determine the expression of IFITM3 protein in 60 HCC samples and paired adjacent tissues. A small interfering RNA fragments of IFITM3 (IFITM3 siRNA) was transiently transfected into HepG2 cells and expressions of IFITM3 at mRNA and protein levels were examined by qRT-PCR and Western blotting. The changes in the proliferation of the transfected cells were determined using cell counting kit 8 (CCK8) assay, and the cell invasion and migration were tested using Transwell assay and wound-healing assay. RESULTS: Compared with the adjacent tissues, HCC tissues expressed significantly higher levels of IFITM3. In HepG2 cells, transfection with IFITM3 siRNA resulted in significant down-regulation of IFITM3 expression at both the protein and mRNA levels and obviously suppressed cell proliferation, invasion, and migration ability as compared with the cells transfected with scrambled siRNA and control cells (P<0.05). CONCLUSIONS: IFITM3, which is overexpressed in HCC, plays a vital role in the proliferation and invasion of HCC cells and may serve as a potential target for gene therapy of HCC.

Preventive and therapeutic effects of quercetin on experimental radiation induced lung injury in mice.

OBJECTIVE: To investigate the protective effect of quercetin on radiation induced lung injury (RILI) and related mechanisms. MATERIALS AND METHODS: Mice treated with radiation and/or quercetin were sacrificed at 1-8 weeks after irradiation under anesthesia. Lung tissues were collected for histological examination. Immunohistochemistry (IHC) and Western blotting were performed to detect the protein expression of nuclear factor-κB (NF-κB) and Mitogen-activated protein kinases (MAPK) pathway. RESULTS: Hematoxylin and eosin (HE) staining showed that radiation controls displayed more severe lung damage than quercetin groups, either high or low dose. Results of IHC and Western blotting demonstrated the expression level of NF-κB to be decreased and that of an inhibitor of NF-κB (Iκb-α) to be increased by the quercetin intervention compared with the radiation control group. Numbers of JNK/SAPK, p38 and p44/p42 positive inflammatory cells were decreased in the radiation+quercetin injection group (P<0.05). CONCLUSIONS: Quercetin may play a radio-protective role in mice lung via suppression of NF-κB and MAPK pathways.

[The clinical effects of complete denture with reducing vertical dimensions in the aged patients].

PURPOSE: To investigate the clinical effects of complete denture with additional 3mm reduction of vertical dimensions in the aged patients. METHODS: Forty edentulous patients with severe resorption of residual ridge were treated with two kinds of complete dentures, i.e. traditional complete denture (TCD) and special complete denture with additional 3mm reduction of vertical dimensions (SCD). After three months of wearing, the masticatory efficiency of dentures were measured by colormetric analysis and the incidences of sore spot was assessed by SAS 6.04 software package. RESULTS: there was no significant difference between TCD and SCD for the masticatory efficiency(P>0.05). But the number of sore spots in SCD was significantly less than that in TCD (P<0.05). CONCLUSION: Complete denture with additional 3mm reduction of vertical dimensions is feasible for clinical practice in the aged patients.

[The survey of puberty timing in healthy boys in Daqing city in northern China].

OBJECTIVE: To investigate the puberty timing in healthy adolescent boys in Daqing city in northern China. METHODS: A cross-sectional and longitudinal combined survey was performed. On 150 male students aged 6-15. Follow up was conducted for 4 years. The serum levels of luteinizing hormone (LH), Follicular Stimulating Hormone (FSH) and total testosterone (TT) were measured. The puberty timing and anthropometry including the body height, weight, and genital development according to Tanner's stages were all recorded. RESULTS: The mean age of puberty onset in healthy adolescent boys is (12.0+/-1.6) years. The growth velocity in the first year after puberty onset is (6.9+/-0.4) cm/year. The level of plasma TT at the time of puberty onset is (1.0+/-0.3) nmol/L. CONCLUSION: The puberty timing of boys in the Daqing city, northern China is in the range from 8 to 14 years.

[Study on the distribution and risk factors of hypertension among children: a cohort study].

OBJECTIVE: To explore the association between hypertension and the tendency of change among children,so as to lay a foundation for the prevention and control of hypertension. METHODS: Based on findings from the prevalence survey that carried out in September 1999 in Daqing of Heilongjiang province. New admission children were selected as subjects to conduct a five-year cohort study. All the subjects were interviewed with questionnaires and their blood specimens were collected for biochemical analysis. All data were analyzed using SPSS 10.0 software. Results The prevalence of hypertension among 447 children was found 2.01% at the baseline study but increased to 5.37% in the fifth year. During a five year period, the systolic pressure level among children increased from (100.65 +/- 11.62)mmHg (1 mm Hg = 0.133 kPa) to (106.67 +/- 9.29) mm Hg,while the diastolic pressure level was from (66.27 +/- 11.31) mm Hg to (70.28 +/- 7.98) mm Hg and showed significant difference between boys and girls. There were association between hypertension and family history, body mass index (BMI), triglyceride, insulin, insulin resistance index while insulin sensitivity index and family history, BMI and insulin sensitivity index appeared to be the important factors. Children under this study were divided to 'with family history or without' and then every group was divided to 'with over weight-obesity or normal'. Obesity and insulin sensitivity seemed the key risk factors on hypertension. Descent of insulin sensitivity was an independent risk factor. CONCLUSION: The level of blood tension among children in Daqing city was higher than that from the national data. The present study confirmed that over-weight,obesity, heredity and insulin resistance were the risk factors of hypertension while insulin resistance was related to hypertension. The interaction of these risk factors was independent or correlated to each other.

[Inhibition of rhodiola on the growth of EVC-304 cell line].

AIM: To observe the effect of rhodiola on human umbilical vein endothelial cell line EVC-304. METHODS: EVC-304 was cultured and divided into two groups: control group and rhodiola-treated group. Three days after treatment, cell survival rate-drug concentration curve was obtained by counting the survival cells, and cells in each group were stained by Wright's stain and observed under microscope. Cell cycle was determined by flow cytometry (FCM). RESULTS: The survival cells in rhodiola-treated group was much less than those in control group. More cells in rhodiola-treated group stayed in G(1) phase while less in S phase when compared with those in control group by FCM. CONCLUSION: Rhodiola can inhibit the growth of human endothelial cell line EVC-304, perhaps through inhibiting the proliferation of the cells. This may lay the foundation for the mechanism study and clinical application of rhodiola in prevention of pulmonary artery hypertension.

[Puberty development of the healthy adolescent girls of Daqing city, Heilongjiang province].

OBJECTIVE: To investigate the process of puberty development of healthy adolescent girls in Northern China. METHODS: 288 adolescent girls of Daqing city, Heilongjiang province, aged 5 to 16, were studied and followed up yearly for four years. The height, weight, fat percentage, second sex characteristics, and the blood levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E(2)) were examined. RESULTS: The mean age of puberty onset of these healthy adolescent girls was 8.5 years +/- 1.1 years. The blood levels of FSH, LH and E(2) were 0.2 mIU/L, 1.1 mIU/L and 0.06 nmol/L respectively (the 95 percentiles were 2.5 mIU/L, 2.3 mIU/L and 0.12 nmol/L respectively). Their mean age of menarche was 12.4 years +/- 1.2 years. The mean age of breast development was 8.8 years +/- 1.1 years. CONCLUSION: The girls in Northern China begin their puberty development at younger ages than reported before.

[Cellular ultrastructural changes of bone marrow of patients with hemorrhagic fever with renal syndrome].

BACKGROUND: To observe cytopathogenic effect of Hantaan virus (HV) on cultured human bone marrow cells. METHODS: Light and transmission electron microscopy and direct immunofluorescent technique were applied to study cellular structure especially ultrastructural changes of bone marrow cells from patients with Hantaan virus infection. Bone marrow cells of one healthy volunteer were also studied as control. RESULTS: The antigen of HV was found in bone marrow cells of 20 of 27 HFRS patients by the aid of direct immunofluorescent technique. It was found that the granulocytes had the highest percentage of HV antigen positive cells (76%), followed by monocytes (65%), lymphocytes (40%), megakaryocytes (20%) and the lowest was found in erythrocytes (3.7%). The injury of cell membrane after infection with HV was significantly more severe than that in the control group under the light and electron microscopy. CONCLUSION: This study demonstrated that HV could attack human bone marrow cells and cause cytopathogenic effect on them.