ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

Objective To observe changes of dynamic functional connectivity(dFC)of brain networks in different stages of Parkinson disease(PD).Methods Totally 52 early-stage PD patients(early PD group),36 late-stage PD patients(late PD group)and 38 healthy controls(HC group)were prospectively enrolled,and resting-state functional MRI were performed.The sliding window,independent component analysis and k-means clustering were used to extract dFC intensity and temporal properties,including fractional windows,dwell time and transition frequency.Results Network connectivity patterns within and between visual network(VIS),sensorimotor network(SMN),default mode network(DMN),cerebellar network(CB)and cognitive executive network(CEN)were altered in PD patients.Four dFC states were identified,in which connections between components in states Ⅰ and Ⅱ were compact,while in states Ⅲ and Ⅳ were sparse.The fractional window and dwell time of late PD group,early PD group and HC group successively increased under state Ⅱ,but successively decreased under state Ⅲ(all P＜0.05).Under state Ⅰ and Ⅳ,no significant difference of fractional window nor dwell time was found between early PD group and late PD group(both P＞0.05),and the above indexes under state Ⅰ were both lower than those in HC group(all P＜0.05),the fraction window under state Ⅳ was higher than that in HC group(both P＜0.05).Conclusion The temporal properties of dFC in PD patients were altered,characterized by increased tendency toward segregated states.Furthermore,fractional windows and dwell time were associated with PD disease stages,suggesting that dFC parameters might serve as novel biomarkers for assessing clinical progression of PD.

Objective To construct a nursing consultation information system based on consultation process and information interaction needs and explore its application effect.Methods The nursing consultation process and information interaction needs were analyzed;the information process,content modules and information interaction interface were designed;the structured records for nursing consultation were developed.The system was officially applied in January 2024.The application effect was evaluated by comparing the completion time of nursing consultations,nursing consultation record quality score,nursing consultation evaluation completion rate,and satisfaction rate before(August 2023 to October 2023)and after(January 2024 to March 2024)the application of the information system.Results After the application of the nursing consultation information system,the implementation rate of nursing consultation for inpatients increased from 1.27％ before the application of the system to 1.47％(P=0.019).The completion time of nursing consultation in the whole hospital reduced from 351(225,421)minutes before the application of the system to 310(156,402)minutes(P＜0.001),and there was a statistically significant difference in the completion time of nursing consultation among the 3 specialties of intravenous therapy,blood purification,and diabetes nursing(P＜0.05).The quality score of nursing consultation records increased from 90.5(82.0,100)points to 95.5(92.0,100)points(P＜0.001).The completion rate of nursing consultation evaluation was higher than those before the system application,with statistical significance(21.6％ vs 78.4％,P＜0.001).Conclusion Nursing consultation information system based on information interaction needs can improve the implementation of nursing consultation for inpatients,shorten the completion time of nursing consultations,improve the writing quality of nursing consultation records and the completion rate of nursing consultation evaluation,and it succeeded in real-time quality monitoring.

Immune thrombocytopenia(ITP)is an autoimmune disease characterized primarily by bleeding and fatigue.ITP-related fatigue can substantially affect health-related quality of life and has been recognized as a treatment indication in the latest guidelines.However,its pathogenesis remains unclear,and targeted therapies are lacking.This paper explores the theoretical foundation of the"excessive fire consuming healthy qi"theory,linking two key conceptual pairs:"excessive fire"with inflammation and"healthy qi consumption"with mitochondrial dysfunction.Chronic inflammation leads to continuous"qi consumption"and damage to mitochondrial structure and function,ultimately resulting in symptoms of qi deficiency such as tiredness and fatigue.The imbalance between qi and fire,leading to imbalance of yin and yang,is the primary pathogenesis of ITP-related fatigue,with the disease mainly affecting the spleen.Considering the etiology and pathogenesis of ITP,and relative equilibrium of yin-yang,the therapeutic approach of invigorating spleen and benefiting qi to promote the production of blood serves as a core treatment strategy.Previous research has demonstrated the clinical efficacy of Jianpi Yiqi Shexue Formula,consisting of milkvetch root,tangshen,Indian bread,largehead atractylodes rhizome,India madder root,and ass hide glue in treating patients with ITP-related fatigue.Designed to invigorate the spleen and regulate qi and blood,this formula aligns with the pathogenesis of ITP-related fatigue characterized by deficiency of spleen qi and stomach qi.The formula also modulates the expression levels of key proteins and genes involved in mitochondrial energy metabolism and alleviates the immune dysfunction.These findings highlight the potential for further research into the mechanism of ITP-related fatigue,particularly by using inflammation-mediated mitochondrial energy metabolism as a promising entry point.

Immune thrombocytopenia(ITP)is an autoimmune disease characterized primarily by bleeding and fatigue.ITP-related fatigue can substantially affect health-related quality of life and has been recognized as a treatment indication in the latest guidelines.However,its pathogenesis remains unclear,and targeted therapies are lacking.This paper explores the theoretical foundation of the"excessive fire consuming healthy qi"theory,linking two key conceptual pairs:"excessive fire"with inflammation and"healthy qi consumption"with mitochondrial dysfunction.Chronic inflammation leads to continuous"qi consumption"and damage to mitochondrial structure and function,ultimately resulting in symptoms of qi deficiency such as tiredness and fatigue.The imbalance between qi and fire,leading to imbalance of yin and yang,is the primary pathogenesis of ITP-related fatigue,with the disease mainly affecting the spleen.Considering the etiology and pathogenesis of ITP,and relative equilibrium of yin-yang,the therapeutic approach of invigorating spleen and benefiting qi to promote the production of blood serves as a core treatment strategy.Previous research has demonstrated the clinical efficacy of Jianpi Yiqi Shexue Formula,consisting of milkvetch root,tangshen,Indian bread,largehead atractylodes rhizome,India madder root,and ass hide glue in treating patients with ITP-related fatigue.Designed to invigorate the spleen and regulate qi and blood,this formula aligns with the pathogenesis of ITP-related fatigue characterized by deficiency of spleen qi and stomach qi.The formula also modulates the expression levels of key proteins and genes involved in mitochondrial energy metabolism and alleviates the immune dysfunction.These findings highlight the potential for further research into the mechanism of ITP-related fatigue,particularly by using inflammation-mediated mitochondrial energy metabolism as a promising entry point.

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.