BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

ObjectiveThe study aimed to evaluate the measurement uncertainty in the determination of five cacaine anesthetics and their metabolites residues by high-performance liquid chromatography-tandem mass spectrometry （LC-MS/MS）. MethodsThrough the establishment of mathematical model， the sources of uncertainty were analyzed， and various components were quantified and synthesized to evaluate the influence of the uncertainty components on the measurement results． ResultsThe uncertainties of the experiments were mainly derived from calibration curve fitting， sample pretreatment， recovery rate， standard solution preparation and measurement repeatability. Furthermore， the expanded uncertainty related to the content in shrimp （k=2） was 1.18 μg‧kg^-1 at 8.68 μg‧kg^-1 for tricaine methanesulfonate （MS-222）， 1.28 μg‧kg^-1 at 9.11 μg‧kg^-1 for benzocaine， 13.5 μg‧kg^-1 at 91.4 μg‧kg^-1 for 4-aminobenzoic acid， 12.2 μg‧kg^-1 at 91.0 μg‧kg^-1 for p-acetylamino benzoic acid， and 11.3 μg‧kg^-1 at 95.3 μg‧kg^-1 for 3-aminobenzoic acid， respectively. ConclusionThis method is suitable for the uncertainty analysis of cacaine anesthetics and their metabolites determination in aquatic products by LC-MS/MS， and can provide scientific and reliable basis for the measurement accuracy.

Objective To explore the effects of mindfulness-based stress reduction ( MBSR ) on anxiety, depression and immune function in patients with gastric cancer .Methods The study investigated 118 patients with gastric cancer who were hospitalized from March 2011 to February 2015 .The participants were randomly divided into the intervention group ( n=59 ) and the control group ( n=59 ) .Both groups received conventional mental health education while the intervention group complemented with MBSR intervention once a week ( six weeks in total ) .Self-rating anxiety scale ( SAS) and self-rating depression scale ( SDS) were used to evaluate patients′anxiety and depression status before and after the intervention .Moreover , T-cell subsets status could reflect the immune function using phosphatase bridging ELISA .Results Before the intervention , the scores of SAS and SDS had no significant differences between the two groups ( P>0.05).However, after the MBSR intervention, the scores for the intervention group significantly reduced and lower than the control group (P<0.05) since the scores for the control group had limited changes (P>0.05).Furthermore, the CD3+, CD4+, CD8 +and CD4+/CD8+had little differences between the two groups before the intervention ( P>0.05) . However , the CD3+, CD4+ and CD4+/CD8+ for the intervention group significantly increased with CD 8+reduced after MBSR (P<0.05), and the differences between the two groups were statistically significant after MBSR(P<0.05), but there were little changes in the control group ( P>0.05).Conclusions The MBSR intervention can significantly reduce the negative emotions such as anxiety and depression , and can increase the immunity in patients with gastric cancer .