Cholestatic liver disease （CLD） is closely associated with bile acid homeostasis imbalance， oxidative stress， inflammatory responses， mitochondrial damage， and hepatic fibrosis. Nuclear factor-erythroid 2-related factor 2 （Nrf2） can regulate molecules related to antioxidation， detoxification， and bile acid transport， and together with signaling pathways such as farnesoid X receptor （FXR）， silent information regulator 1/AMP-activated protein kinase， and nuclear factor-κB， participates in the development and progression of CLD. This review summarizes the role of Nrf2 in the development and progression of CLD， as well as the research progress on traditional Chinese medicine （TCM） active constituents and formulas/Chinese patent medicine in regulating Nrf2 for the intervention of CLD. The results indicate that TCM active constituents such as terpenoids， saponins， flavonoids， and polysaccharides， as well as formulas/Chinese patent medicine with the effects of heat-clearing and dampness-draining， liver-soothing and choleretic-promoting， and body-strengthening and liver-protecting， can improve bile acid metabolism and transport and alleviate oxidative stress， inflammatory responses， and hepatic fibrosis by regulating Nrf2-related signaling pathways. However， existing studies still primarily judge based on Nrf2 expression， nuclear translocation， and downstream molecular expression changes， and the understanding of the regulatory relationship between Nrf2 and signaling pathways such as FXR， as well as the synergistic mechanisms of multiple constituents in formulas， remains insufficient. Future studies can strengthen gene intervention and functional validation， utilize liver or bile duct organoids， co-culture systems， and other approaches， and combine bile acid profiling and multi-omics analysis to further elucidate the mechanism by which TCM regulates Nrf2 to ameliorate CLD.

ObjectiveTo clarify the independent and synergistic effects of dyslipidemia in the progression of hepatic steatosis in metabolic dysfunction-associated fatty liver disease （MAFLD）. MethodsA total of 7 697 participants who underwent physical examination in Beijing Friendship Hospital， Capital Medical University， from January 2022 to December 2024 were enrolled， and finally 2 177 patients with MAFLD were enrolled as subjects. Transient elastography was used to quantify the severity of hepatic steatosis （grades S1-S3）. The multivariable ordinal Logistic regression analysis was used to investigate the independent and synergistic associations of serum triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） with the severity of hepatic steatosis， and their interactions and potential nonlinear relationships with metabolic factors were also examined. One-way analysis of variance or Kruskal-Wallis H test was used for comparison of continuous data between groups， and chi-square test was used for comparison of categorical data between groups. ResultsAn increase in TG （odds ratio ［OR］=1.77， 95% confidence interval ［CI］： 1.48 — 2.10， P<0.001） and a reduction in HDL-C （OR=1.35， 95%CI： 1.11 — 1.65， P=0.003） were independently associated with a greater severity of hepatic steatosis， with the strongest association when both abnormalities coexisted （OR=2.40， 95%CI： 1.87 — 3.07， P<0.001）. The dose-response relationship analysis further revealed a nonlinear threshold effect of TG on hepatic steatosis at the threshold of 1.51 mmol/L （P_nonlinearity=0.001）， below which the severity of steatosis increased more rapidly with the increase in TG concentration （P=0.001）. The subgroup analysis showed that the association between the reduction in HDL-C and the severity of steatosis was observed only in males， young adults （aged <45 years）， and metabolically healthier subgroups （without diabetes， obesity， hyperuricemia or hypertension）. Significant interactions were observed between the presence or absence of obesity and the abnormal levels of TG and HDL‑C （both P_interaction<0.05）. The association of the increase in LDL-C with steatosis was confined to specific subgroups （without obesity or hyperuricemia）. ConclusionThe increase in TG and the reduction in HDL-C are independently associated with the severity of hepatic steatosis in MAFLD. The synergistic effect of blood lipids and their interactions with metabolic factors may further refine risk stratification， so as to provide a basis for precise management of MAFLD.

Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.

The National Institute on Aging-Alzheimer's Association(NIA-AA)released the"Revised criteria for diagnosis and staging of Alzheimer's disease"in 2024,representing a significant update following the 2011 and 2018 frameworks.This new standard aims to advance Alzheimer's disease diagnosis and treatment from a"clinical-pathological"model to a"precision biology"era,improving early diagnosis rates and guiding precise therapeutic interventions.Nuclear medicine molecular imaging plays an irreplaceable role in Alzheimer's disease diagnosis and staging,with key updates in the 2024 standard being the replacement of traditional clinical diagnosis with biological definitions and the hierarchical classification of biomarkers.This article focuses on interpreting the core positioning and clinical application value of multimodal imaging technologies within the new standard framework,particularly the critical roles of amyloid β-protein PET and tau PET in early diagnosis,biological staging and treatment monitoring of Alzheimer's disease,aiming to provide guidance for clinical practice.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

Objective:This current study aims to explore the approaches for constructing a professional clinical research system within the context of research ward development, with the ultimate objective of providing valuable guidance for the establishment and development of proficient clinical research teams.Methods:Through a comprehensive case analysis, integrating the practical experiences from clinical trials conducted in the research ward of a Class-A tertiary hospital in Beijing, along with an extensive review of relevant literature and policy studies, this paper examined the current state of domestic clinical research implementation teams. Subsequently, a series of strategies were devised to build and foster professional clinical research teams and to explore corrective measures for cultivating a dynamic professional clinical research talent ecosystem.Results:The development of full-time clinical research teams in China was rather slow, and there was a lack of mature clinical trial teams training blueprints. Drawing on the practical experience accumulated during the establishment of a professional clinical research team in a leading hospital in Beijing, it was crucial to attach utmost importance to the optimal allocation of human and material resources. This required the systematic training of principal investigators, coordinating researchers, and research assistants, as well as the setting up of a comprehensive support system, an advanced scientific research team, and a quality control unit. Moreover, the standardization of operational models of both domestic and foreign research institutions, along with the implementation of corresponding support and incentive mechanisms, and the strengthening of training and continuing education frameworks were equally significant.Conclusions:During the process of assembling a full-time clinical research team, it is of utmost significance to cultivate professional principal investigators, coordinating researchers, and research assistants. Complemented by the establishment of a comprehensive support team, a scientific research team, and a quality control team, along with corresponding support and incentive mechanisms, this is crucial for constructing a professional clinical research execution team and a sustainable talent ecosystem in the research ward. Eventually, this will drive the efficient and high-quality progress of China's pharmaceutical industry.

Objective To compare the effect of cold therapy at different temperature on the pain and motor function of delayed onset muscle soreness(DOMS)in the upper limbs of young men.Methods From April to July,2024,24 healthy young men(aged 22 to 26 years)were selected from the Key Laboratory of Winter Sports Technical Diagnosis and Skill Evaluation of the General Administration of Sport of China at Shenyang Sport University,and randomly divided into control group,group A and group B equally.An isokinetic muscle strength testing system was used to establish a DOMS movement model for elbow joint.Then,group A re-ceived cold therapy at a constant temperature of 10℃for 10 minutes,group B received cold therapy at a con-stant temperature of 6℃for 10 minutes,and the control group received natural recovery.They were measured relative peak torque(rPT)of the elbow flexor muscles at angular velocities of 60°/s,120°/s and 180°/s with iso-kinetic muscle strength testing system,and root mean square(RMS)of EMG amplitude of biceps brachii was synchronously collected using a wireless surface EMG system,immediately,and 24,48 and 72 hours after model establishment;while,they were assessed with Visual Analogue Scale(VAS)for pain.Results The main effects of VAS score,rPT and RMS were significant in both intra-group(F>15.716,P<0.001)and inter-group(F>6.478,P<0.01).At 24,48 and 72 hours after model establishment,the VAS scores showed a trend of control group>group A>group B(P<0.05).Although the pairwise comparison results of rPT and RMS among the groups varied at different time points after model establishment under different angular veloci-ties,overall,rPT presented a trend of control groupgroup A>group B(P<0.05).The higher the angular velocity and the longer the time,the more obvious this trend was.Conclusions Cold therapy can relieve the pain of DOMS in the upper limbs of young men and promote the recovery of muscle strength,especially at a constant temperature of 6℃.

Objective:To establish a predictive model for the risk of cognitive impairment in patients with hypertension.Methods:Data were obtained from the China Health and Retirement Longitudinal Study(CHARLS),and 17 indicators were analyzed,including demographic features,behavioral factors,and health status.The study cohort was randomly divided into a training set(n=2 918)and an internal validation set(n=1 249)at a ratio of 7∶3,and 1 457 patients with hypertension who were treated in Chongqing Traditional Chinese Medicine Hospital from January to December 2024 were included as an external validation set.The least absolute shrinkage and selection operator regression analysis was used to identify predictive variables,and 10-fold cross-validation was used to determine the optimal model.A logistic regression model was used to investigate the risk factors for cognitive impairment in patients with hypertension,and then a nomogram prediction model was established.The calibration curve was used to assess the accuracy of the model,and the area under the ROC curve(AUC)and the decision curve analysis were used to assess the predictive performance of the model.Results:A total of 4167 hypertensive patients aged≥45 years were included from the CHARLS database,among whom 668 had cognitive impairment.The multivariate logistic regression analysis showed that age(odds ratio[OR]=1.408,95%CI=1.040-1.056),sex(OR=0.570,95%CI=0.492-0.660),body mass index(OR=0.931,95%CI=0.914-0.948),educational level(OR=0.235,95%CI=0.200-0.277),place of residence(OR=1.674,95%CI=1.447-1.936),physi-cal activity(OR=0.459,95%CI=0.373-0.562),depression(OR=1.386,95%CI=1.198-1.604),and total cholesterol level(OR=0.997,95%CI=0.995-0.999)were predictive variables.The ROC curve analysis showed that the nomogram model had good performance,with an AUC of 0.814(95%CI=0.802-0.826)in the training set,0.817(95%CI=0.788-0.846)in the internal validation set,and 0.725(95%CI=0.699-0.752)in the external validation set.Conclusion:The nomogram model developed in this study can effectively predict the risk of cognitive impairment in Chinese patients with hyperten-sion and has a good application value.

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

Volumes 9 and 10 of Sun Simiao's Supplement to Important Formulas Worth a Thousand Gold Pieces record part of Trea-tise on Cold Damage,which contain Sun Simiao's unique thoughts on six-meridian treatment.Sun Simiao's treatment of Taiyang me-ridian emphasizes the classification of prescriptions and syndromes,advocates the correct treatment methods,and establishes three guidelines;Yangming meridian emphasizes the differentiation of cold and heat syndromes;except Taiyang meridian,all meridians em-phasize the differentiation of outline syndromes.It has made important contributions to the inheritance and development of the six-me-ridian thought of Treatise on Cold Damage in later generations.