ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

Objective To investigate the expression level and clinical significance of circular RNAs(circRNAs)in serum extracellular vesicles(EVs)of patients with recurrent spontaneous abortion(RSA).Methods The serum samples from 3 RSA patients and 3 nor-mal pregnant women(controls)visited our hospital from May 2021 to March 2023 were collected and the gene expression profiling chips were used to screen for differentially expressed circRNAs in serum EVs.Ten RSA patients and 10 normal pregnant women were enrolled in a training set and 80 RSA patients and 64 normal pregnant women were enrolled in a validation set.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of differentially expressed circRNAs between the two groups.The predictive value of differentially expressed circRNAs for RSA was evaluated by the receiver operating characteristic(ROC)curve.Results A total of 57 563 circRNAs in serum EVs were detected by the gene expression profiling chips.Compared with the control group,3 516 circRNAs were differentially expressed in RSA patients,including 2 377 up-regulated and 1 139 down-regulated.The de-tection results of qRT-PCR in the training set and validation set showed that the expression levels of hsa＿circ＿0054403 in serum EVs of RSA patients(2.07[1.00,6.68])was significantly higher than that in the control group(1.00[0.42,1.46],U=1 239,P＜0.01),while those of hsa＿circ＿0020897(0.33[0.11,1.40]vs 1.00[0.46,3.66],U=1 712,P＜0.01)and hsa＿circ＿0072745(0.49[0.22,1.60]vs 1.00[0.51,7.93],U=1 714,P＜0.01)were significantly lower than that in the control group.The ROC curve showed that the hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs had high predictive value for RSA.Their AUCROC were 0.758,0.666,and 0.664,respectively,and the corresponding sensitivity and specificity were 47.5% and 100.0%,50.0% and 81.2%,and 62.5% and 70.3%,respectively.When the three circRNAs were combined,it's AUCROC,sensitivity,and specificity were 0.842,73.7%,and 79.7%,respectively.Conclusion The hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs of RSA patients are abnormally expressed,which may serve as the potential markers for predicting RSA.

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

ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

Objective:To investigate the predictive value of the triglyceride-high-density lipoprotein cholesterol-glucose-body mass index (TyHGB) and triglyceride-glucose-body mass index (TyG-BMI) in early pregnancy for gestational diabetes mellitus (GDM) and pregnancy outcomes.Methods:A retrospective analysis was conducted, a total of 600 pregnant women who underwent prenatal examinations at North China Medical and Health Group Xingtai General Hospital from August 2020 to August 2023 were collected. Participants were divided into GDM group (76 cases) and non-GDM group (524 cases) based on GDM occurrence, and further categorized into adverse pregnancy group (101 cases) and favorable pregnancy group (499 cases) based on outcomes. Multivariate Logistic regression was used to identify risk factors for GDM and adverse pregnancy. The predictive performance of TyHGB and TyG-BMI was evaluated using receiver operating characteristic (ROC) curves.Results:After adjusting for confounders, TyHGB and TyG-BMI were independent risk factors for GDM ( OR = 1.569, 95% CI 1.259 -1.955; OR = 1.109, 95% CI 1.029 - 1.038) and adverse pregnancy ( OR = 1.438, 95% CI 1.193 - 1.734; OR = 1.021, 95% CI 1.014 - 1.029). The area under the curve (AUC) for TyHGB and TyG-BMI alone in predicting GDM was 0.677 and 0.731, respectively. Combined prediction of GDM yielded an AUC of 0.793, with sensitivity of 72.37% and specificity of 65.81%. For adverse pregnancy, the AUC of TyHGB and TyG-BMI alone were 0.666 and 0.692, respectively, while their combination achieved AUC of 0.746, with specificity of 69.34% and sensitivity of 65.35%. Conclusions:TyHGB and TyG-BMI in early pregnancy are risk factors for GDM and adverse pregnancy outcomes. Their combination can enhance predictive efficacy for both conditions.

Purpose To evaluate the value of 3D amide proton transfer imaging(3D APT)and reduced field-of-view diffusion weighted imaging(rFOV DWI)in predicting histologic grade of rectal adenocarcinoma.Materials and Methods A total of 64 cases of rectal adenocarcinoma confirmed by pathology were analyzed from February 2020 to April 2023,with 28 cases in the high and 36 cases in the medium-low differentiation group,retrospectively.MRI sequences including reduced field-of-view high-resolution T2WI(rFOV T2WI),rFOV DWI and 3D APT before surgery.Two neuroradiologists delineated the solid part of the tumor layer by layer,and extracted its apparent diffusion coefficient(ADC)and magnetization transfer ratio asymmetry(MTRasym)values.Combined-parameter model(MTRasym+rADC)was constructed by binary Logistic regression.The efficacy of the single-parameter and combined-parameter model was assessed using receiver operating characteristic curve.Results The mean value of MTRasym of the medium-low group[(2.93±0.61)%]was higher than that of high differentiation group[(1.74±0.63)%](t=-7.60,P＜0.001),and the mean value of rADC of the medium-low group[(0.98±0.17)×10-3 mm2/s]was lower than that of the high differentiation group[(1.19±0.18)×10-3 mm2/s](t=4.50,P＜0.001).In the identification of histopathological grades of rectal adenocarcinoma,receiver operating characteristic analysis showed that compared with MTRasym and rADC,the combined parameter model had the highest diagnostic performance,with an area under the curve of 0.94,sensitivity and specificity of 0.86 and 0.96.Conclusion 3D APT and rFOV DWI are helpful in identifying the histopathological grade of rectal adenocarcinoma.

Objective To investigate the expression level and clinical significance of circular RNAs(circRNAs)in serum extracellular vesicles(EVs)of patients with recurrent spontaneous abortion(RSA).Methods The serum samples from 3 RSA patients and 3 nor-mal pregnant women(controls)visited our hospital from May 2021 to March 2023 were collected and the gene expression profiling chips were used to screen for differentially expressed circRNAs in serum EVs.Ten RSA patients and 10 normal pregnant women were enrolled in a training set and 80 RSA patients and 64 normal pregnant women were enrolled in a validation set.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of differentially expressed circRNAs between the two groups.The predictive value of differentially expressed circRNAs for RSA was evaluated by the receiver operating characteristic(ROC)curve.Results A total of 57 563 circRNAs in serum EVs were detected by the gene expression profiling chips.Compared with the control group,3 516 circRNAs were differentially expressed in RSA patients,including 2 377 up-regulated and 1 139 down-regulated.The de-tection results of qRT-PCR in the training set and validation set showed that the expression levels of hsa＿circ＿0054403 in serum EVs of RSA patients(2.07[1.00,6.68])was significantly higher than that in the control group(1.00[0.42,1.46],U=1 239,P＜0.01),while those of hsa＿circ＿0020897(0.33[0.11,1.40]vs 1.00[0.46,3.66],U=1 712,P＜0.01)and hsa＿circ＿0072745(0.49[0.22,1.60]vs 1.00[0.51,7.93],U=1 714,P＜0.01)were significantly lower than that in the control group.The ROC curve showed that the hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs had high predictive value for RSA.Their AUCROC were 0.758,0.666,and 0.664,respectively,and the corresponding sensitivity and specificity were 47.5% and 100.0%,50.0% and 81.2%,and 62.5% and 70.3%,respectively.When the three circRNAs were combined,it's AUCROC,sensitivity,and specificity were 0.842,73.7%,and 79.7%,respectively.Conclusion The hsa＿circ＿0054403,hsa＿circ＿0020897,and hsa＿circ＿0072745 in serum EVs of RSA patients are abnormally expressed,which may serve as the potential markers for predicting RSA.

Purpose To evaluate the value of 3D amide proton transfer imaging(3D APT)and reduced field-of-view diffusion weighted imaging(rFOV DWI)in predicting histologic grade of rectal adenocarcinoma.Materials and Methods A total of 64 cases of rectal adenocarcinoma confirmed by pathology were analyzed from February 2020 to April 2023,with 28 cases in the high and 36 cases in the medium-low differentiation group,retrospectively.MRI sequences including reduced field-of-view high-resolution T2WI(rFOV T2WI),rFOV DWI and 3D APT before surgery.Two neuroradiologists delineated the solid part of the tumor layer by layer,and extracted its apparent diffusion coefficient(ADC)and magnetization transfer ratio asymmetry(MTRasym)values.Combined-parameter model(MTRasym+rADC)was constructed by binary Logistic regression.The efficacy of the single-parameter and combined-parameter model was assessed using receiver operating characteristic curve.Results The mean value of MTRasym of the medium-low group[(2.93±0.61)%]was higher than that of high differentiation group[(1.74±0.63)%](t=-7.60,P＜0.001),and the mean value of rADC of the medium-low group[(0.98±0.17)×10-3 mm2/s]was lower than that of the high differentiation group[(1.19±0.18)×10-3 mm2/s](t=4.50,P＜0.001).In the identification of histopathological grades of rectal adenocarcinoma,receiver operating characteristic analysis showed that compared with MTRasym and rADC,the combined parameter model had the highest diagnostic performance,with an area under the curve of 0.94,sensitivity and specificity of 0.86 and 0.96.Conclusion 3D APT and rFOV DWI are helpful in identifying the histopathological grade of rectal adenocarcinoma.