Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Objective To investigate the therapeutic effects of a newly constructed Aβ25-35-based recombinant gene vaccine for Alzheimer's disease(AD).Methods The pcDNA-Aβ25-35-GRP94 recombinant gene vaccine was con-structed using Aβ25-35 as the epitope and pcDNA3.1 plasmid as the vector.Early APP/PS1 double-transgenic mice were selected as experimental subjects,including the AD control group and the pcDNA-Aβ25-35-GRP94 immunized group for regular immunization.ELISA was performed to detect the titers and isotypes of Aβ-specific antibodies;Morris Water Maze(MWM)Test and Open-Field Test(OFT)were performed to determine the changes in both cognitive ability and mental state of mice;Immunohistochemistry was used to assess the effects of the vac-cine on both Aβ plaques and glial cells in the brains of AD mouse models;ELISA kit was used to evaluate the level of inflammatory factors(TNF-α,IL-1β)in the mouse brain.Results Compared with the AD control group,the pcDNA-Aβ25-35-GRP94 vaccine induced APP/PS1 mice to produce higher levels of Aβ specific antibodies(P<0.05),and mainly induced IgG1 antibodies(P<0.01).The vaccine significantly reduced Aβ plaques in the brain tissue(P<0.05)and effectively alleviated learning memory impairment in APP/PS1 mice(P<0.05)without causing mental behavioral abnormalities.Moreover,the vaccine inhibited the abnormal proliferation of glial cells(P<0.05)and did not cause obvious inflammatory reactions in the brain,suggesting the vaccine was safe and effective.Conclusions Early vaccination with a Aβ25-35-based recombinant gene vaccine can induce the formation of high level of Aβ specific antibodies,effectively alleviate the learning memory impairment of AD and related neu-ro-pathological changes.It may be used to treat AD.

Objective To understand the changing trend of nutritional status of children undergoing liver transplantation within 6 months after discharge,and to explore its influencing factors,in order to provide guidance for the clinical formulation of personalized nutritional intervention programs.Methods By the convenient sampling method,153 children undergoing liver transplantation admitted to the liver transplantation center of a tertiary A hospital in Hangzhou from January 2023 to January 2024 were selected as the research subjects.Their basic and clinical data were collected.The nutritional status at the 1 day before surgery and 1 month,3 months,and 6 months after discharge was evaluated by the standard deviation evaluation method of children's nutritional status.According to the changing trend of their nutritional status,they were grouped.Univariate and multivariate Logistic regression were used to analyze the influencing factors of the changing trend of nutritional status in children undergoing liver transplantation.Results A total of 144 children who underwent liver transplantation were ultimately included in the study.The incidence of malnutrition at 1 month,3 months,and 6 months after discharge was 66.0％,54.9％,and 53.5％,respectively.According to the changing trend of nutritional status of children undergoing liver transplantation,they were divided into 3 groups:54 cases(37.5％)in the good nutritional status group,24 cases(16.7％)in the fluctuating nutritional status group,and 66 cases(45.8％)in the poor nutritional status group.The results of multivariate Logistic regression analysis showed that birth weight,feeding method within 6 months after birth,age of caregivers and learning situation of nutritional knowledge were the influencing factors of the changing trend of nutritional status in children undergoing liver transplantation(P＜0.05).Conclusion The incidence of malnutrition in children undergoing liver transplantation is high within 6 months after discharge;medical staff should closely collaborate with families to formulate and implement staged personalized nutritional intervention measures based on the specific conditions and influencing factors of the children to effectively improve the nutritional status of the children after transplantation.

Deficiencies remain in the early identification and screening method for type 2 diabetes mellitus(T2DM).Relying solely on blood glucose indicators as diagnostic criteria fails to capture the systematic evolution of glucose metabolism destabilization and does not allow for the identification of the critical transition period preceding the onset of T2DM.In the complex system of the human body,structural and state variables correspond to the traditional Chinese medicine concepts of"zang"and"xiang."These variables determine the landscape of the systemic state changes over time.The pathogenesis of T2DM is characterized by a shift from compensatory insulin secretion to β-cell dysfunction,driven by negative-positive feedback dynamics,ultimately resulting in a marked increase in blood glucose levels.A critical transition exists between glycemic homeostasis and the establishment of T2DM disease homeostasis.Using theoretical approaches such as critical slowing and dynamic network markers in dynamical systems theory,various clinical case data-including four-diagnosis information,multiple biological samples,and histological analysis method-can be leveraged to identify the critical transition key stage from pre-disease to disease of T2DM,facilitating early intervention.This paper aims to develop a dynamic model describing the transition from"glucose homeostasis-glycemic state of instability-steady state of T2DM"by analyzing the mechanism of the complex human system and the dynamic characteristics underlying T2DM onset.This framework aims to enhance early identification method.Establishing this holistic approach offers a novel perspective for the prevention and treatment of T2DM.

Objective To understand the changing trend of nutritional status of children undergoing liver transplantation within 6 months after discharge,and to explore its influencing factors,in order to provide guidance for the clinical formulation of personalized nutritional intervention programs.Methods By the convenient sampling method,153 children undergoing liver transplantation admitted to the liver transplantation center of a tertiary A hospital in Hangzhou from January 2023 to January 2024 were selected as the research subjects.Their basic and clinical data were collected.The nutritional status at the 1 day before surgery and 1 month,3 months,and 6 months after discharge was evaluated by the standard deviation evaluation method of children's nutritional status.According to the changing trend of their nutritional status,they were grouped.Univariate and multivariate Logistic regression were used to analyze the influencing factors of the changing trend of nutritional status in children undergoing liver transplantation.Results A total of 144 children who underwent liver transplantation were ultimately included in the study.The incidence of malnutrition at 1 month,3 months,and 6 months after discharge was 66.0％,54.9％,and 53.5％,respectively.According to the changing trend of nutritional status of children undergoing liver transplantation,they were divided into 3 groups:54 cases(37.5％)in the good nutritional status group,24 cases(16.7％)in the fluctuating nutritional status group,and 66 cases(45.8％)in the poor nutritional status group.The results of multivariate Logistic regression analysis showed that birth weight,feeding method within 6 months after birth,age of caregivers and learning situation of nutritional knowledge were the influencing factors of the changing trend of nutritional status in children undergoing liver transplantation(P＜0.05).Conclusion The incidence of malnutrition in children undergoing liver transplantation is high within 6 months after discharge;medical staff should closely collaborate with families to formulate and implement staged personalized nutritional intervention measures based on the specific conditions and influencing factors of the children to effectively improve the nutritional status of the children after transplantation.

The "pre-disease" theory of traditional Chinese medicine focuses on the dynamic and continuous evolution from health to disease, and emphasizes early identification and intervention in the complex and gradual process of evolution from health to disease. The "pre-disease" theory and complexity science share the same perspective on health and disease from the standpoint of features of the dynamic evolution and holism, i. e., life is considered as a complex system with ongoing dynamic changes, which exhibit the nonlinear features of " homeostasis-destabilization-phase transition-another homeostasis". In this paper, from the perspective of nonlinear dynamics in complexity science, we explain the scientific connotation of the evolution law of "pre-disease"-disease based on the theory of critical slowing down in traditional Chinese medicine. Based on the theory of critical slowing down and the dynamic network biomarker method generated by its development, combined with the macro signs of comprehensive analysis of data gained by four diagnostic method and the micro features including transcriptomics and the microbiomics, this paper proposes to integrate macro and micro multi-hierarchy information to construct a "pre-disease" critical slowing down identification model with the characteristics of traditional Chinese medicine diagnosis and treatment, which provides a new perspective and method for the early warning of complex diseases.

Objective To study the effect of Ditan Decoction combined with aripiprazole and olanzapine in the treatment of schizophrenia and its influence on serum inflammatory factors chnage.Methods Seventy-seven patients with schizophrenia meeting the requirements visiting the outpatient department and hospitalized in Dazu District Hospital of Traditional Chinese Medicine and Dazu District Mental Health Center from July 2021 to March 2023 were selected as the study subjects and divided into the observation group(n=38)and control group(n=39).The control group was treated with aripiprazole and olanzapine,and the observation group was combined with Ditan Decoction on the basis of the control group.After 8 weeks of treatment,the TCM syndrome scores,Positive and Negative Syndrome Scale(PANSS)score,serum inflammatory factors(IL-6,IL-1β,IL-17)levels were compared between the two groups.Results The total effective rate was 97.37％in the observation group and 84.65％in the control group,and the difference was statistically signifi-cant(P＜0.05).The TCM syndrome score of each item and total scores after treatment in the observation group were lower than those in the control group(P＜0.05),the PANSS positive symptoms,negative symp-toms,general psychopathology and total scores in the observation group were lower than those in the control group(P＜0.05).The IL-17,IL-6 and IL-1β levels after treatment in observation group were lower than those in the control group(P＜0.05).Conclusion Ditan Decoction combined with aripiprazole and olanzapine has significant clinical efficacy in the treatment of schizophrenia,which could further reduce the symptom score of the patients and improve the serum inflammatory factors levels.The treatment is highly safe and worthy of clinical recommendation.

Objective To generate a stable kidney-specific deletion of augmenter of liver regeneration(ALR)mice and provide an animal model for further studying the biological function of ALR in the kidney.In addition,we further explored the effect of ALR on renal tubulointerstitial fibrosis.Methods Mating and identification of ALRflox/+/Ggt1-Cre mice with ALRflox/flox mice was carried out,and the ALRflox/flox/Ggt1-Cre mice were screened.Mating and identification of ALRflox/flox/Ggt1-Cre mice with ALRflox/flox mice were carried out,and screening the ALRflox/flox/Ggt1-Cre mice was performed.The ALRflox/flox/Ggt1-Cre mouse was a kidney-specific ALR knockout mouse and the ALRflox/flox mouse was a control mouse.The mouse genotypes were identified by PCR;the expression of ALR protein and mRNA levels in mouse liver were detected by Western blotting and real-time PCR;ALR expression in mouse kidney was detected by immunofluorescence.The kidney tissue morphology of the mouse kidney was observed using hematoxylin-eosin staining,periodic acid Schiff's reaction and Masson stain.Flow cytometry,immunohistochemistry,immunofluorescence and real time PCR analyses were used to determine macrophage phenotype.Results PCR results indicate that mouse genotypes are consistent with ALRflox/flox/Ggt1-Cre.Compared with ALRflox/flox mice,ALRflox/flox/Ggt1-Cre mice showed lower levels of ALR mRNA and protein,more interstitial inflammatory cells in kidney tissue,broken basement membrane of the renal tubules,the brush-border damage and significant interstitial fibrosis.After the kidney-specific ALR gene was knocked out,macrophages infiltrated the kidney tissue o and the polarization process of macrophages from M1 to M2 was reduced.Conclusion In this study,the kidney-specific deletion of ALR mouse was successfully constructed using the Cre/Loxp technology,which providing an important animal model for further study of the role of ALR genes.And ALR deficiency promotes renal fibrosis in physiological conditions.

Objective To generate a stable kidney-specific deletion of augmenter of liver regeneration(ALR)mice and provide an animal model for further studying the biological function of ALR in the kidney.In addition,we further explored the effect of ALR on renal tubulointerstitial fibrosis.Methods Mating and identification of ALRflox/+/Ggt1-Cre mice with ALRflox/flox mice was carried out,and the ALRflox/flox/Ggt1-Cre mice were screened.Mating and identification of ALRflox/flox/Ggt1-Cre mice with ALRflox/flox mice were carried out,and screening the ALRflox/flox/Ggt1-Cre mice was performed.The ALRflox/flox/Ggt1-Cre mouse was a kidney-specific ALR knockout mouse and the ALRflox/flox mouse was a control mouse.The mouse genotypes were identified by PCR;the expression of ALR protein and mRNA levels in mouse liver were detected by Western blotting and real-time PCR;ALR expression in mouse kidney was detected by immunofluorescence.The kidney tissue morphology of the mouse kidney was observed using hematoxylin-eosin staining,periodic acid Schiff's reaction and Masson stain.Flow cytometry,immunohistochemistry,immunofluorescence and real time PCR analyses were used to determine macrophage phenotype.Results PCR results indicate that mouse genotypes are consistent with ALRflox/flox/Ggt1-Cre.Compared with ALRflox/flox mice,ALRflox/flox/Ggt1-Cre mice showed lower levels of ALR mRNA and protein,more interstitial inflammatory cells in kidney tissue,broken basement membrane of the renal tubules,the brush-border damage and significant interstitial fibrosis.After the kidney-specific ALR gene was knocked out,macrophages infiltrated the kidney tissue o and the polarization process of macrophages from M1 to M2 was reduced.Conclusion In this study,the kidney-specific deletion of ALR mouse was successfully constructed using the Cre/Loxp technology,which providing an important animal model for further study of the role of ALR genes.And ALR deficiency promotes renal fibrosis in physiological conditions.

OBJECTIVE To compare anti-ischemic stroke （IS） effect of different extraction parts from Gastrodia elata， and to provide reference for screening the anti-IS effective parts of G. elata. METHODS G. elata was extracted and separated by ethanol reflux extraction and ethyl acetate extraction. The rat model of diffuse cerebral thrombosis was induced by internal carotid artery injection of arachidonic acid （AA）； the anti-IS effect of G. elata powder， ethanol extract of G. elata， residue of ethanol extract of G. elata， ethyl acetate extract of G. elata， residue of ethyl acetate extract of G. elata， gastrodin and aspirin （positive control drug） were investigated with the content of Evans blue （EB） in the ischemic brain tissue as index. RESULTS Compared with model group， aspirin， ethanol extract of G. elata and ethyl acetate extract of G. elata could significantly decrease the content of EB in the ischemic brain tissue of model rats （P＜0.05）. G. elata powder had the tendency to reduce the content of EB in the ischemic brain tissue of model rats， without statistical significance （P＞0.05）. The residue of ethanol extract of G. elata， residue of ethyl acetate extract of G. elata and gastrodin had little effect on the content of EB in the ischemic brain tissue of model rats. CONCLUSIONS Both ethanol extract of G. elata and ethyl acetate extract of G. elata have anti-IS effects， which are stronger than that of G. elata powder.