Steroid-induced osteonecrosis of the femoral head (SONFH) is avascular necrosis of the femoral head caused by long-erm use of corticosteroids, and its pathogenesis is complex and affected by changes in the dynamic balance of the bone microenvironment. With the deepening of research, the role of bone microenvironment in the pathogenesis of SONFH has been gradually revealed. In the case of excessive use of glucocorticoids (GCs), the bone microenvironment changes significantly, causing imbalance in bone lipid metabolism, microcirculation disorders and disorders of immune regulation, which promotes the increase of the number and activity of osteoclasts, and interferes with the differentiation of osteoblasts and adipoblasts. Through the regulation of PI3K/AKT, OPG/RANKL/RANK, MAPK, JAK/STAT, Hedgehog and other signaling pathways, it eventually leads to osteocyte apoptosis, bone microvascular rupture and destruction of trabecular bone structure, which in turn leads to osteonecrosis, bone density reduction and bone microstructure destruction due to bone microcirculation ischemia, and finally leads to necrosis of the femoral head. This article reviews the role of bone microenvironment homeostasis in GCs-induced ONFH and the regulatory mechanism of bone microenvironment, which is helpful to reveal the pathogenesis of SONFH and provide a theoretical basis for exploring effective intervention strategies.
Humans ; Femur Head Necrosis/physiopathology* ; Animals ; Signal Transduction ; Bone and Bones/metabolism* ; Glucocorticoids/adverse effects* ; Cellular Microenvironment

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To explore the clinical rational use evaluation method for high-value medical consumables in diagnosis related groups(DRG)using association rules in order to provide references for the supervision of clinical rational use of high-value medical consumables.Methods The cardiovascular department was taken as an example.Firstly,K-means algorithm was applied to cluster analysis of DRG cases in the department,and representative cases were selected as the research objects;secondly,Apriori algorithm was used to mine the frequent item sets of DRG patient groups,the high-value medical consumables in the department and the rules of association between DRG patient groups and medical consumables;finally,two indicators of the importance of regulation and rationality of the use of medical consumables were designed to evaluate the importance of regulation and rationality of the use of high-value medical consumables.Results There were two common DRG patient groups in the cardiovascular department,including FM39 percutaneous cardiac catheterization and FM19 percutaneous coronary stent implantation,and the frequently used medical consumables contained vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire in the two groups.The common combinations of medical consumables used in the FM39 DRG patient group comprised of vascular sheath,contrast catheter,pressure monitoring kit,triple three-way stopcock and coronary guide wire,which were close to that of the cardiovascular department;there were some additional consumables involved in the common combinations in the FM19 group such as occluder,coronary guide catheter,pressure pump,drug-eluting stent and coronary dilation balloon.The top three medical consumables in terms of regulatory importance were cutting balloon,coronary guide wire and drug-eluting stent;using the confidence level from January to September 2022 as a reference,from January to September 2023 the rationality of using high-value consumables in FM39 group went higher by 5.08％while that in FM19 group went lower by 9.23％.Conclusion The association rule-based evaluation method for the use of medical consumables in DRG patient groups can be used for assessing the importance of regulation and rationality of the use of high-value medical consumables,which provides references for the supervision of clinical rational use of high-value medical consumables.[Chinese Medical Equipment Journal,2024,45(11):67-71]

Objective:To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism(Ta-VTE),and to study the risk factors for Ta-VTE.Methods:The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled,and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor.The differences in clinical data and laboratory indicators between the two groups were analyzed,and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE.Results:A total of 288 patients with VTE were included in this study,including 64 cases in Ta-VTE group and 224 cases in pure VTE group,respectively.There were significant differences in the following indexes between the two groups,including the hospitalization time(14.20±15.29 d vs 10.05±6.90 d,t=3.112,P=0.002),pain(35.94％vs 65.18％,x2=17.554,P=0.000),recent surgery(75.00％vs 37.50％,X2=28.196,P=0.000),D-dimer[2.8(0.92,7.55)μg/ml vs 5.69(2.25,13.91)μg/ml,Z=-2.710,P=0.007],PLR[198.59(139.54,312.16)vs 149.76(114.08,233.66),Z=-2.924,P=0.003]and TBIL[10.90(7.63,15.68)μmol/Lvs 12.90(9.33,18.28)μmol/L,Z=-2.066,P=0.039].There was no significant difference in the other indicators(P＞0.05).The result of multivariate logistic regression analysis showed that elevated PLR(OR=1.003,95％CI:1.000-1.006,P=0.027),recent surgery(OR=4.312,95％CI:2.093-8.885,P=0.000)and prolonged hospitalization(OR=1.037,95％CI:1.002-1.074,P=0.038)were independent risk factors for Ta-VTE.However,pain(OR=0.274,95％CI:0.133-0.564,P=0.000)was a protective factor.Conclusion:Elevated PLR level,recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients,and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.