In recent years,more and more researches has focused on the correlation between cognitive activity and physiological variables.The change of pupil is regarded as an important target in the cognitive process,and has become a hot research field.This review focuses on the three key brain regions that regulate pupil change,and reflects the neurophysiological mechanism behind pupil change by elaborating the neural pathways related to pupil change and cognitive performance.Based on recent studies on pupil change in cognitive diseases,it aims to promote the application of pupil change in the field of cognitive science in the future.

Objective To retrospectively analyze the association between metabolic factors and high-risk colorectal adenoma(CRA).Methods The medical records of patients aged 18-75 years who underwent their initial colonoscopy at Karamay Central Hospital of Xinjiang Uygur Autonomous Region from Jul 2000 to Mar 2017 were collected.The comparison between normal colonoscopy(NC)and high-risk CRA patients was conducted using an unpaired t-test,while chi-square test was used for categorical variables.Least absolute shrinkage and selection operator(LASSO)regression and Logistic regression were utilized to analyze the association between metabolic factors and high-risk CRA.Results A total of 1 798 patients meeting the inclusion and exclusion criteria were enrolled and divided into normal colonoscopy(NC)findings group(n=972)and high-risk CRA group(n=826).The high-risk CRA group exhibited significantly lower levels of high-density lipoprotein cholesterol(HDL-C)in comparison to the NC group,while uric acid and fibrosis 4(FIB-4)index levels were significantly higher than those observed in the NC group(all P<0.05).Based on LASSO regression analysis,we identified 12 variables that potentially influence the occurrence of high-risk CRA,including age,gender,smoking history,alcohol consumption history,non-alcoholic fatty liver disease(NAFLD),hypertension,coronary artery disease,hyperglycemia,hypercholesterolemia,low levels of HDL-C,elevated alanine aminotransferase,and elevated gamma-glutamyl transferase.Multivariate analysis revealed that individuals aged over 50 years,male gender,cigarette and alcohol consumption,low HDL-C levels,history of NAFLD and hypertension were identified as independent risk factors associated with high-risk CRA(P<0.05).In addition,without or with adjusting for age,sex,smoking,and drinking history,patients with a high TG/HDL-C ratio(the ratio≥2.68)had a significantly higher risk of high-risk CRA than those with a low TG/HDL-C ratio(the ratio<2.68)[odds ratios(ORs)were1.430 and 1.235 respectively,all P<0.05)].Without or with adjusting variables,the ORs for NAFLD patients with FIB-4 index>2.67 were 1.849(P=0.466)and 1.435(P=0.707),respectively.Conclusion A significant association exists between metabolic factors and high-risk CRA.Independent risk factors for high-risk CRA include older age(≥50 years),male,smoking history,alcohol consumption history,low levels of HDL-C,and a history of NAFLD and hypertension.Individuals exhibiting a TG/HDL-C ratio exceeding 2.68 manifest a significantly heightened susceptibility to the development of high-risk CRA.Therefore,elderly males with one or more aforementioned metabolic abnormalities should be considered a priority population for colorectal screening.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

Objective To retrospectively analyze the association between metabolic factors and high-risk colorectal adenoma(CRA).Methods The medical records of patients aged 18-75 years who underwent their initial colonoscopy at Karamay Central Hospital of Xinjiang Uygur Autonomous Region from Jul 2000 to Mar 2017 were collected.The comparison between normal colonoscopy(NC)and high-risk CRA patients was conducted using an unpaired t-test,while chi-square test was used for categorical variables.Least absolute shrinkage and selection operator(LASSO)regression and Logistic regression were utilized to analyze the association between metabolic factors and high-risk CRA.Results A total of 1 798 patients meeting the inclusion and exclusion criteria were enrolled and divided into normal colonoscopy(NC)findings group(n=972)and high-risk CRA group(n=826).The high-risk CRA group exhibited significantly lower levels of high-density lipoprotein cholesterol(HDL-C)in comparison to the NC group,while uric acid and fibrosis 4(FIB-4)index levels were significantly higher than those observed in the NC group(all P<0.05).Based on LASSO regression analysis,we identified 12 variables that potentially influence the occurrence of high-risk CRA,including age,gender,smoking history,alcohol consumption history,non-alcoholic fatty liver disease(NAFLD),hypertension,coronary artery disease,hyperglycemia,hypercholesterolemia,low levels of HDL-C,elevated alanine aminotransferase,and elevated gamma-glutamyl transferase.Multivariate analysis revealed that individuals aged over 50 years,male gender,cigarette and alcohol consumption,low HDL-C levels,history of NAFLD and hypertension were identified as independent risk factors associated with high-risk CRA(P<0.05).In addition,without or with adjusting for age,sex,smoking,and drinking history,patients with a high TG/HDL-C ratio(the ratio≥2.68)had a significantly higher risk of high-risk CRA than those with a low TG/HDL-C ratio(the ratio<2.68)[odds ratios(ORs)were1.430 and 1.235 respectively,all P<0.05)].Without or with adjusting variables,the ORs for NAFLD patients with FIB-4 index>2.67 were 1.849(P=0.466)and 1.435(P=0.707),respectively.Conclusion A significant association exists between metabolic factors and high-risk CRA.Independent risk factors for high-risk CRA include older age(≥50 years),male,smoking history,alcohol consumption history,low levels of HDL-C,and a history of NAFLD and hypertension.Individuals exhibiting a TG/HDL-C ratio exceeding 2.68 manifest a significantly heightened susceptibility to the development of high-risk CRA.Therefore,elderly males with one or more aforementioned metabolic abnormalities should be considered a priority population for colorectal screening.

Objective To observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

Objective To observe the therapeutic efficacy and mechanism of Gushi Zaizao Pills for steroid-induced osteonecrosis of the femoral head(SONFH).Methods Male SD rats were randomly divided into normal group,model group,Xianling Gubao Capsules group and Gushi Zaizao Pills group.Except for the normal group,the rats in all other groups were replicated the SONFH model.After successful modeling,the continuous drug administration was carried out for six weeks.The thymus and spleen of the rats were taken to calculate the immune organ indices,the contents of interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α)in rat synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA),the percentage of empty lacunae and area ratio of trabecular bone was detected by hematoxylin-eosin(HE)staining,and the femoral head parameters[reduction of bone volume fraction(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)]were analyzed by Micro-CT,and bone strength of femoral head was detected by small animal bone strength tester.Results Compared with the normal group,the spleen and thymus indicators were significantly decreased in the model group,the levels of IL-1β and TNF-α in rat synovial fluid were significantly increased,the percentage of empty lacunae was increased,the area ratio of trabecular bone was decreased,the BV/TV,Tb.N and Tb.Th were decreased,the Tb.Sp was increased,the bone strength of femoral head was significantly decreased,the differences being all statistically significant(P＜0.05 or P＜0.01).Compared with the model group,the spleen and thymus indicators were significantly increased in Xianling Gubao Capsules group and Gushi Zaizao Pills group,the levels of IL-1β and TNF-α in rat synovial fluid were decreased,the percentage of empty lacunae was significantly decreased,the area ratio of trabecular bone was significantly increased,the BV/TV,Tb.N and Tb.Th were increased,the Tb.Sp was decreased,and the bone strength of femoral head was significantly increased,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Gushi Zaizao Pills can effectively prevent the further development of SONFH by regulating cellular immunity and reducing the secretion of inflammatory factors,thereby reducing the pathological damage of the femoral head and enhancing the bone strength.

ObjectiveTo observe the changes in the expression and distribution of G protein-gated inwardly rectifying potassium channel subunit 2 （GIRK2） in the dorsal root ganglion （DRG） and spinal cord dorsal horn of rats with remifentanil-induced hyperalgesia. MethodsHyperalgesia was induced by intravenous infusion of remifentanil 4 μg/kg/min for 2 h in adult male SD rats. At 6th hour and on days 1， 3 and 5 following remifentanil treatment， we used immunofluorescence to examine the changes in the GIRK2 distribution and expression. Immunoblotting was used to detect GIRK2 expression of the total protein and membrane protein in DRG and spinal dorsal horn of rats. Behavioral testing was applied to evaluate the effect of intrathecal injection of GIRK2-specific agonist ML297 on thermal nociceptive threshold on day 1 after remifentanil infusion. Resultsmmunofluorescence results showed that GIRK2 was mainly co-localized with IB4-positive small neurons in DRG and nerve fibers in spinal dorsal horn. GIRK2 expression was significantly downregulated following remifentanil treatment. Immunoblotting results revealed that on day 1 following intravenous infusion of remifentanil， compared with those in the control group， GIRK2 expression levels of the total protein and membrane protein in DRG （0.47 ± 0.10 vs. 1.01 ± 0.17， P < 0.001； 0.47 ± 0.11 vs. 1.06 ± 0.12， P < 0.001） and spinal dorsal horn （0.52 ± 0.09 vs. 1.10 ± 0.08， P < 0.001； 0.54 ± 0.10 vs. 1.01 ± 0.13， P < 0.001） were all significantly decreased. The behavioral results showed that intrathecal ML297 effect on thermal withdrawal latency was significantly reduced following remifentanil treatment （P < 0.001）. ConclusionsRemifentanil might induce hyperalgesia via down-regulating GIRK2 expression in rat DRG and spinal cord dorsal horn.

In the context of Pharma 4.0, the design tools that support the pharmaceutical Quality by Design(QbD) are iterating fast toward intelligent or smart design. The conventional development methods for traditional Chinese medicine(TCM) preparations have the limitations such as over dependence on experience, low dimensions for the designed experiment parameters, poor compatibility between the process and equipment, and high trial-and-error cost during process scale-up. Therefore, this paper innovatively proposed the intelligent co-design involving material, process, and equipment for manufacturing high-quality TCM preparations, and introduced the design philosophy, targets, tools, and applications with TCM oral solid dosage(OSD) as an example. In terms of design philosophy, the pharmaceutical design tetrahedron composed of critical material attributes, critical process parameters, critical equipment attributes, and critical quality attributes was developed. The design targets were put forward based on the product performance classification system. The design tools involve a design platform that contains several modules, such a as the iTCM material database, the processing route classification system, the system modeling and simulation, and reliability-based optimization. The roles of different modules in obtaining essential and universal design knowledge of the key common manufacturing units were introduced. At last, the applications of the co-design methodology involving material, process, and equipment in the high shear wet granulation process development and the improvement of the dissolving or dispersion capability of TCM formula granules are illustrated. The research on advanced pharmaceutical design theory and methodology will help enhance the efficiency and reliability of drug development, improve the product quality, and promote the innovation of high-end TCM products across the industry.
Medicine, Chinese Traditional ; Reproducibility of Results ; Quality Control ; Computer Simulation ; Commerce ; Pharmaceutical Preparations ; Drugs, Chinese Herbal