Allergic rhinitis(AR)affects 10%-40%of the population in the world.Because CLOCK genes regulate the circadian rhythms of AR,the symptoms in parts of the patients are aggravated in the morning and evening and relieved at moon.Although lots of studies showed that traditional Chinese medicine is effective for AR,further explores are still needed to analyze the circadian rhythm of AR based on Chinese Chronological Medicine for controlling the circadian outbreak point of symptoms of AR in daily cycle.We supposed that Weiyang might play an important role for controlling the circadian rhythm of AR with closed similarities with the tidal variation of the expressions of CLOCK genes.Thus based on Weiyang theory,we tried to clarify the mechanism of circadian rhythm of AR and explore the relationship between Weiyang and the CLOCK genes so as to further expand the treatment methods of adjusting the circadian cycle of AR with TCM and improve the corresponding therapeutic efficacy.

OBJECTIVE To investigate the pharmacodynamics and related mechanisms of Anmei Dan on hippocampus of mice with coronary heart disease complicated with depression.METHODS The coronary heart disease model combined with chronic and unpredictable mild stress depression model was established,and the mice were randomly divided into blank group,model group,low dose group(1.5 g·kg-1),high dose group(3 g·kg-1)and atorvastatin group(0.3 g·kg-1).Sucrose preference test,open field test and forced swimming test were used to evaluate the behavioral changes of mice.qPCR and ELISA were employed to ascertain the mR-NA expression of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumour necrosis factor-α(TNF-α)in the hippocampus.The changes of neurons and Nissl bodies in CA1,CA3 and DG regions of hippocampus were observed by Nissl staining.The expression of key proteins was detected by Western blot.RESULTS Compared with the blank group,the sucrose preference rate of mice in the model group was decreased(P<0.01),the forced swimming immobility time was extended(P<0.01)and the movement distance in the open field experiment was not significantly changed.The levels of total cholesterol(TC),triglyceride(TG)and low density lipopro-tein cholesterol(LDL-C)were increased significantly(P<0.01)and the level of high density lipoprotein cholesterol(HDL-C)was decreased significantly(P<0.01).The mRNA level and content of IL-1β,IL-6 and TNF-α were significantly increased(P<0.01).The expression of glutamate receptor 1(GluR1),postsynaptic densitin-95(PSD-95),brain-derived neurotrophic factor(BDNF)and phosphorylated calmodulin-dependent kinase(p-CaMKⅡ)in hippocampus was decreased(P<0.01).The expression of cytoskeletal activity regulatory protein(Arc)was increased(P<0.01).In the model group,the cell structure was irregular and differ-ent degrees of damage occurred,the Nissl bodies decreased or disappeared,and the cell membrane broke.Compared with the model group,the sucrose preference rate of mice in each administration group was significantly increased(P<0.01),the immobility time in forced swimming experiment was significantly decreased(P<0.01),and the levels of TC,TG and LDL-C of mice in Anmei Dan groups and atorvastatin group were decreased(P<0.01),while the level of HDL-C increased(P<0.01).The mRNA levels and con-tent of IL-1β,IL-6 and TNF-α in Anmei Dan groups and atorvastatin group were decreased(P<0.01).The expression of GluR1,PSD-95,BDNF and p-CaMKⅡ in hippocampal tissue of Anmei Dan groups were increased(P<0.01),and the expression of Arc was decreased(P<0.01).The morphology and structure of the cells in the Anmei Dan group and the atorvastatin group were improved,with varying degrees of increased Nissl bodies and relatively intact cell membranes.CONCLUSION Anmei Dan can effectively im-prove blood lipids and depression-like behavior of coronary heart disease mice complicated with depression.It can inhibit pro-inflam-matory factors,increase the expression of neurotrophic factors,effectively improve synaptic related proteins,and reduce the damage to neurons,thus effectively preventing the exacerbation of coronary heart disease and depression comorbidity.

OBJECTIVE:Prolonged sedentary behavior can acutely reduce peripheral and central vascular function,thereby increasing the risk of cardiovascular disease.Interrupting sedentary behavior may be a potential practical strategy to prevent vascular dysfunction caused by prolonged sitting.However,current research findings on its acute effects are inconsistent,and specific application recommendations have not yet been established.This study aims to perform a Meta-analysis on the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults and to explore its regulatory factors.METHODS:Following PRISMA reporting guidelines,literature search was conducted in March 2024 using the keywords of"interrupting,""sedentary,"and"vascular function"in the Web of Science Core Collection,PubMed,and China National Knowledge Infrastructure(CNKI)databases.Acute randomized crossover trials addressing the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults were included.Risk of Bias 2 developed by Cochrane was used to assess bias risk,and the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)system was used to evaluate the evidence level.The"meta"and"metaphor"packages in R(version 4.2.0)were used for main effect aggregation(Hedge's g acted as the effect size indicator),publication bias testing,subgroup analysis,and regression analysis.RESULTS:Twenty-two randomized crossover trials involving 364 subjects(aged 21 to 70 years)were included.Meta-analysis results showed that compared with prolonged sitting,interrupting sedentary behavior acutely improved peripheral vascular blood flow volume(Hedge's g=0.48,95%confidence interval:0.14-0.82,P<0.01,I2=63%,low evidence level),shear stress(Hedge's g=0.65,95%confidence interval:0.37-0.93],P<0.01,I2=54%,moderate evidence level),and flow-mediated dilation(Hedge's g=0.43,95%confidence interval:0.15-0.72,P<0.01,I2=61%,moderate evidence level).Disease had a significant moderating effect on the main effect aggregation for blood flow volume(P=0.01 between subgroups),while the mode(P=0.01 between subgroups)and frequency(P=0.02 between subgroups)of interruptions had significant moderating effects on shear stress.Improvements in peripheral vascular shear stress from interrupting sedentary behavior were affected by age(β=-0.02,95%confidence interval:-0.03-0.01,P=0.09)and body mass index(β=-0.10,95%confidence interval:-0.18 to-0.02,P<0.01).Improvements in flow-mediated dilation were influenced by the total number of interruptions(β=-0.09,95%confidence interval:-0.17 to-0.01,P=0.03)and the duration of sitting during the control period(β=-0.21,95%confidence interval:-0.34 to-0.09,P<0.01).Each additional hour of sitting was associated with a 0.67%reduction in the acute improvement effect of flow-mediated dilation from interrupting sedentary behavior(P<0.01),and acute benefits disappeared when sitting control time exceeded 6 hours.A qualitative systematic review found that interrupting sedentary behavior did not significantly affect pulse wave velocity in various populations but could effectively prevent central vascular function decline in older adults due to prolonged sitting.CONCLUSION:Interrupting sedentary behavior acutely improves peripheral vascular blood flow volume(low evidence level),shear stress(moderate evidence level),and flow-mediated dilation(moderate evidence level)in adults and may prevent or protect against central vascular function decline in older adults due to prolonged sitting(very low evidence level).Characteristics of subjects(disease factors,sex,age,and body mass index),interruption intervention schemes(mode,frequency,total number of interruptions),and duration of sitting control all influence the acute improvement effects of interrupting sedentary behavior on vascular function.It is recommended that adults interrupt sedentary behavior with exercises involving large muscle groups,such as stair climbing,at high frequencies(e.g.,once every 40 minutes)with at least 5 minutes of moderate-to low-intensity activity each time,and limit the cumulative duration of prolonged sitting to no more than 6 hours per day.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

OBJECTIVE To investigate the pharmacodynamics and related mechanisms of Anmei Dan on hippocampus of mice with coronary heart disease complicated with depression.METHODS The coronary heart disease model combined with chronic and unpredictable mild stress depression model was established,and the mice were randomly divided into blank group,model group,low dose group(1.5 g·kg-1),high dose group(3 g·kg-1)and atorvastatin group(0.3 g·kg-1).Sucrose preference test,open field test and forced swimming test were used to evaluate the behavioral changes of mice.qPCR and ELISA were employed to ascertain the mR-NA expression of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumour necrosis factor-α(TNF-α)in the hippocampus.The changes of neurons and Nissl bodies in CA1,CA3 and DG regions of hippocampus were observed by Nissl staining.The expression of key proteins was detected by Western blot.RESULTS Compared with the blank group,the sucrose preference rate of mice in the model group was decreased(P<0.01),the forced swimming immobility time was extended(P<0.01)and the movement distance in the open field experiment was not significantly changed.The levels of total cholesterol(TC),triglyceride(TG)and low density lipopro-tein cholesterol(LDL-C)were increased significantly(P<0.01)and the level of high density lipoprotein cholesterol(HDL-C)was decreased significantly(P<0.01).The mRNA level and content of IL-1β,IL-6 and TNF-α were significantly increased(P<0.01).The expression of glutamate receptor 1(GluR1),postsynaptic densitin-95(PSD-95),brain-derived neurotrophic factor(BDNF)and phosphorylated calmodulin-dependent kinase(p-CaMKⅡ)in hippocampus was decreased(P<0.01).The expression of cytoskeletal activity regulatory protein(Arc)was increased(P<0.01).In the model group,the cell structure was irregular and differ-ent degrees of damage occurred,the Nissl bodies decreased or disappeared,and the cell membrane broke.Compared with the model group,the sucrose preference rate of mice in each administration group was significantly increased(P<0.01),the immobility time in forced swimming experiment was significantly decreased(P<0.01),and the levels of TC,TG and LDL-C of mice in Anmei Dan groups and atorvastatin group were decreased(P<0.01),while the level of HDL-C increased(P<0.01).The mRNA levels and con-tent of IL-1β,IL-6 and TNF-α in Anmei Dan groups and atorvastatin group were decreased(P<0.01).The expression of GluR1,PSD-95,BDNF and p-CaMKⅡ in hippocampal tissue of Anmei Dan groups were increased(P<0.01),and the expression of Arc was decreased(P<0.01).The morphology and structure of the cells in the Anmei Dan group and the atorvastatin group were improved,with varying degrees of increased Nissl bodies and relatively intact cell membranes.CONCLUSION Anmei Dan can effectively im-prove blood lipids and depression-like behavior of coronary heart disease mice complicated with depression.It can inhibit pro-inflam-matory factors,increase the expression of neurotrophic factors,effectively improve synaptic related proteins,and reduce the damage to neurons,thus effectively preventing the exacerbation of coronary heart disease and depression comorbidity.

Allergic rhinitis(AR)affects 10%-40%of the population in the world.Because CLOCK genes regulate the circadian rhythms of AR,the symptoms in parts of the patients are aggravated in the morning and evening and relieved at moon.Although lots of studies showed that traditional Chinese medicine is effective for AR,further explores are still needed to analyze the circadian rhythm of AR based on Chinese Chronological Medicine for controlling the circadian outbreak point of symptoms of AR in daily cycle.We supposed that Weiyang might play an important role for controlling the circadian rhythm of AR with closed similarities with the tidal variation of the expressions of CLOCK genes.Thus based on Weiyang theory,we tried to clarify the mechanism of circadian rhythm of AR and explore the relationship between Weiyang and the CLOCK genes so as to further expand the treatment methods of adjusting the circadian cycle of AR with TCM and improve the corresponding therapeutic efficacy.

OBJECTIVE:Prolonged sedentary behavior can acutely reduce peripheral and central vascular function,thereby increasing the risk of cardiovascular disease.Interrupting sedentary behavior may be a potential practical strategy to prevent vascular dysfunction caused by prolonged sitting.However,current research findings on its acute effects are inconsistent,and specific application recommendations have not yet been established.This study aims to perform a Meta-analysis on the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults and to explore its regulatory factors.METHODS:Following PRISMA reporting guidelines,literature search was conducted in March 2024 using the keywords of"interrupting,""sedentary,"and"vascular function"in the Web of Science Core Collection,PubMed,and China National Knowledge Infrastructure(CNKI)databases.Acute randomized crossover trials addressing the acute effects of interrupting sedentary behavior on peripheral and central vascular function in adults were included.Risk of Bias 2 developed by Cochrane was used to assess bias risk,and the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)system was used to evaluate the evidence level.The"meta"and"metaphor"packages in R(version 4.2.0)were used for main effect aggregation(Hedge's g acted as the effect size indicator),publication bias testing,subgroup analysis,and regression analysis.RESULTS:Twenty-two randomized crossover trials involving 364 subjects(aged 21 to 70 years)were included.Meta-analysis results showed that compared with prolonged sitting,interrupting sedentary behavior acutely improved peripheral vascular blood flow volume(Hedge's g=0.48,95%confidence interval:0.14-0.82,P<0.01,I2=63%,low evidence level),shear stress(Hedge's g=0.65,95%confidence interval:0.37-0.93],P<0.01,I2=54%,moderate evidence level),and flow-mediated dilation(Hedge's g=0.43,95%confidence interval:0.15-0.72,P<0.01,I2=61%,moderate evidence level).Disease had a significant moderating effect on the main effect aggregation for blood flow volume(P=0.01 between subgroups),while the mode(P=0.01 between subgroups)and frequency(P=0.02 between subgroups)of interruptions had significant moderating effects on shear stress.Improvements in peripheral vascular shear stress from interrupting sedentary behavior were affected by age(β=-0.02,95%confidence interval:-0.03-0.01,P=0.09)and body mass index(β=-0.10,95%confidence interval:-0.18 to-0.02,P<0.01).Improvements in flow-mediated dilation were influenced by the total number of interruptions(β=-0.09,95%confidence interval:-0.17 to-0.01,P=0.03)and the duration of sitting during the control period(β=-0.21,95%confidence interval:-0.34 to-0.09,P<0.01).Each additional hour of sitting was associated with a 0.67%reduction in the acute improvement effect of flow-mediated dilation from interrupting sedentary behavior(P<0.01),and acute benefits disappeared when sitting control time exceeded 6 hours.A qualitative systematic review found that interrupting sedentary behavior did not significantly affect pulse wave velocity in various populations but could effectively prevent central vascular function decline in older adults due to prolonged sitting.CONCLUSION:Interrupting sedentary behavior acutely improves peripheral vascular blood flow volume(low evidence level),shear stress(moderate evidence level),and flow-mediated dilation(moderate evidence level)in adults and may prevent or protect against central vascular function decline in older adults due to prolonged sitting(very low evidence level).Characteristics of subjects(disease factors,sex,age,and body mass index),interruption intervention schemes(mode,frequency,total number of interruptions),and duration of sitting control all influence the acute improvement effects of interrupting sedentary behavior on vascular function.It is recommended that adults interrupt sedentary behavior with exercises involving large muscle groups,such as stair climbing,at high frequencies(e.g.,once every 40 minutes)with at least 5 minutes of moderate-to low-intensity activity each time,and limit the cumulative duration of prolonged sitting to no more than 6 hours per day.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Based on the theory of engineering medicine,a consensus which takes the basic medical ethics of harm reduction as the starting point is proposed to addresses the current clinical problems of a wide variety of radiotherapy setup equipments and methods,large differences by principles,and inaccurate setup.The consensus is formed in two aspects.(1)Advocate coordination of multiple setup methods for joint setup;collect,compare,analyze and screen data on setup methods;determine the operational guidelines and methods for joint setup based on the principle of standardized and unified clinical consistency,with a view to achieving the clinical purpose of greatly ensuring the precision of radiotherapy setup and radiotherapy safety without relying on the golden standard.(2)Standardize the operational methods for tracing setup deviations,so that when the difference in setup leads to poor clinical consistency,the cause of deviation can be traced and the effectiveness of different setups can be screened.Based on the concept of engineering medicine,the consensus is expected to standardize the method of radiotherapy setup,realize accurate radiotherapy,improve treatment effect and show medical ethical care.