This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.