Objective to explore the correlation between interferon-γ receptor(IFNGR)2 amino acid sites Val14Met and GIn64Arg polymorphism and atherosclerosis plaque stability in Yunnan Han nationality.Methods The patients with unstable atherosclerotic plaque in our hospital from March 2014 to March 2015 were collected as the observation group and contemporaneous patients with stable atherosclerotic plaque/non-plaque as the control group.The peripheral venous blood was collected for extracting genomic DNA.IFNGR Va114Met and GIn64Arg loci genotype was detected by the PCR product direct sequencing method.The sequencing results were analyzed by adopting the DNAStar and GeneTool software.The levels of plasma cytokines(IFN-γ)was detected by the flow cytometry.Results Two hundreds and four native Han patients were included in this study,including the observation group,109 cases,age(76.89±12.08)years old;the control group,95 cases,age(65.99±16.32)years old.The polymorphism change of IFNGR1 Vall4Met loci was not found irn the two groups.In the observation group,the frequency of IFNGR2 Gln64Arg genotype AA was 51.95％(40/77),which of AGwas 53.06 ％(52/98)and which of GG was 58.62％(17/29);in the control group,the frequencies were 48.05 ％ (37/77),46.94 ％ (46/98) and 41.38 ％ (12/29),chi-square test,P =0.824.The IFNGR2 Gln64Arg genotypes AA,AG and GG had no relation with atherosclerotic plaque stability.The A and G allele frequencies in the observation group were 52.38％ (132/252)and 55.13 ％ (86/156)respectively,which of the control group were 47.62 ％ (120/252)and 44.87％ (70/156),chi-square test's P=0.661.The IFNGR2 Gln64Arg A/G allele had no relation with atherosclerotic plaque stability.By Hardy-Weinberg genetic balance test,the gene frequency in this sample population was in accordance with the genetic equilibrium law.The plasma IFN-γ level in the observation group was(4.60 ± 1.91)ng/mL,which in the control group was (4.88 ± 2.10)ng/ mL,the difference was not statistically significant(P=0.318);the plasma IFN-γ content had no relation with atherosclerotic plaque stability(P=0.308).Conclusion The genetic polymorphisms of IFNGR can not serve as a warning indicator of atherosclerotic plaque stability.

Oxytocin ( OT ) is a cyclic neuropeptide containing nine amino acids residues, in addition to the traditional roles of uterine contraction and lactation, it also plays important roles in the central nervous system and other peripheral organs, such as improving schizophrenia, autism - related psychiatric and psy-chological symptoms. Oxytocin exhibits its physiological func-tions by binding to its receptor (oxytocin receptor,OTR). Cur-
rently researchers are manipulating OT system by developing new OTR ligand ( agonists and antagonists ) , hoping to prevent and treat OTR related diseases. This paper reviews the latest devel-opment of OTR agonists, antagonists and its physiological roles in central nerve system and peripheral organs.

G protein-coupled receptors (GPCRs) are the largest cell surface receptor family, which mediates activities of almost all known cellular response to ligands, including hormones release, neurotransmitters and sensory input.GPCRs can promote development and progression of gastric cancer, colorectal cancer, lung cancer and breast cancer and other tumors.Tyrosine kinase receptors (RTKs) are another important family of membrane receptors, which can regulate cell proliferation, differentiation, migration and survival.Overexpression of RTKs has been found in many cancer cells.Therefore, GPCRs and RTKs are equally important in the clinical treatment of cancer therapeutic.However, GPCRs and RTKs are not independent, and they can use common signal transduction.The present study show that crosstalk between GPCRs and RTKs can facilitate migration of lung epithelial cells, increasing survival of nerve cells and promoting tumor occurrence and development.This article mainly focuses on crosstalk between GPCRs and RTKs and their roles in tumorigenesis and oncotherapy.

JNK is a key protein in the third stages of MAPK pro-tein kinase activation cascade,and is located in the key node of multiple signal transduction network.It plays a pivotal role in the cell proliferation,differentiation,apoptosis and some other important cell biological processes.Therefore it acts as an im-portant factor in regulating the development of some major human diseases,such as cancer.But the functional diversity and com-plexity of three JNK isoforms in different cell types make it diffi-
cult to develop anticancer drugs with JNK as a treatment target. In this review,we summarized the apoptotic signaling network of JNK and the regulation functions of JNK in cell apoptosis and proliferation.We also discuss the different functions of 3 JNK isoforms in human cancer.

Objective To study the protective effect of Panax notoginseng saponins(PNS)and its components Rg1 and Rb1 on oxygen-glucose deprivation/reoxygenation(OGD/Reox)-induced tight junction damage. Methods Anaerobic box were used to induce OGD in HUVEC cells for 6 h followed by reoxygenation for 24 h. Transepithelial/endothelial electrical resistance(TEER)and cell permeability were detected,immunefluorescence was used to observe the ZO-1 and claudin-5 protein expression. Results PNS 20,40 mg/L and ginsenoside Rb1 significantly inhibited the OGD/Reox-induced decreased tight junction resistance,and the increased cell permeability(P< 0.05). PNS 20,40 mg/L and ginsenoside Rb1 partly restored the inter-cellular tight junctions which were regularly arranged on the cell membrane, and the cells displayed cobble stone-like arrangement. Conclusions PNS ameliorates ischemia-induced vascular endothelial cell tight junction damage via MMP-9 and VEGF/VEGFR2 signaling pathway. Rb1 is one of the effective monomer components.

Aging is a significant risk factor for various diseases, including asthma, and it often leads to poorer clinical outcomes, particularly in elderly individuals. It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage, resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases. The effects of aging affect not only the elderly but also those of younger ages, posing significant challenges to global healthcare. Thus, understanding the molecular mechanisms associated with aging in different diseases is essential. One intriguing factor is the aryl hydrocarbon receptor (AhR), which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process. Here, we review the literature on several major hallmarks of aging, including mitochondrial dysfunction, cellular senescence, autophagy, mitophagy, epigenetic alterations, and microbiome disturbances. Moreover, we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures, particularly in relation to the immune system. Furthermore, we explore how aging hallmarks affect clinical characteristics, inflammatory features, exacerbations, and the treatment of asthma. It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.
Humans ; Aged ; Receptors, Aryl Hydrocarbon/metabolism* ; Asthma ; Aging ; Gene Expression Regulation ; Ligands

BACKGROUND: Early fluid resuscitation is one of the fundamental treatments for acute pancreatitis (AP), but there is no consensus on the optimal fluid rate. This systematic review and meta-analysis aimed to compare the efficacy and safety of aggressive vs. controlled fluid resuscitation (CFR) in AP. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science databases were searched up to September 30, 2022, for randomized controlled trials (RCTs) comparing aggressive with controlled rates of early fluid resuscitation in AP patients without organ failure on admission. The following keywords were used in the search strategy: "pancreatitis," "fluid therapy,""fluid resuscitation,"and "randomized controlled trial." There was no language restriction. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the certainty of evidence. Trial sequential analysis (TSA) was used to control the risk of random errors and assess the conclusions. RESULTS: A total of five RCTs, involving 481 participants, were included in this study. For primary outcomes, there was no significant difference in the development of severe AP (relative risk [RR]: 1.87, 95% confidence interval [CI] 0.95-3.68; P = 0.07; n = 437; moderate quality of evidence) or hypovolemia (RR: 0.98, 95% CI: 0.32-2.97; P = 0.97; n = 437; moderate quality of evidence) between the aggressive and CFR groups. A significantly higher risk of fluid overload (RR: 3.25, 95% CI: 1.53-6.93; P <0.01; n = 249; low quality of evidence) was observed in the aggressive fluid resuscitation (AFR) group than the controlled group. Additionally, the risk of intensive care unit admission ( P = 0.02) and the length of hospital stay ( P <0.01) as partial secondary outcomes were higher in the AFR group. TSA suggested that more studies were required to draw precise conclusions. CONCLUSION: For AP patients without organ failure on admission, CFR may be superior to AFR with respect to both efficacy and safety outcomes. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; CRD 42022363945.
Humans ; Randomized Controlled Trials as Topic ; Fluid Therapy ; Hypovolemia ; Pancreatitis/therapy*