ObjectiveTo observe the clinical efficacy and safety of hot ironing with Haitongpi Formula （海桐皮方， HF） in the treatment of lumbar disc herniation （LDH） of cold-dampness obstruction type. MethodsA total of 70 patients with cold-dampness obstruction type LDH were randomly divided into a treatment group and a control group， with 35 cases in each group. Both groups received three movements technique of Qinggong Spinal Manipulation （QSM） as the basis for treatment. In addition， the treatment group received hot ironing with HF， while the control group applied Diclofenac Sodium Gel externally. The treatment duration for both groups was 14 days. The clinical efficacy was compared between groups. Japanese Orthopedic Association （JOA） score， visual analog scale （VAS） for pain， pain pressure threshold （PPT） for lumbar positive response points， and traditional Chinese medicine （TCM） symptom scores were compared， on day 7， and day 14 of treatment， as well as on day 7 and day 14 of follow-up. The lumbar curvature index （LCI） was also compared before treatment and on day 14 of treatment. Adverse reactions during the study were recorded for both groups. ResultsA total of 35 patients in the treatment group and 34 patients in the control group were included for final analysis. The clinical total effective rate of the treatment group （91.43%， 32/35） was significantly higher than that of the control group （82.35%， 28/34， P＜0.05）. Both the JOA score and PPT of the two groups increased on day 7 and day 14 of treatment， and on day 7 and day 14 of follow-up. VAS scores and TCM symptom scores both decreased. The LCI of both groups increased on day 14 of treatment （P＜0.01）. Compared with the control group at the same time points， on day 14 of treatment and day 7 and day 14 of follow-up， the treatment group had higher JOA scores and PPT， and lower VAS scores and TCM symptom scores. The LCI of the treatment group increased on day 14 of treatment （P＜0.05 or P＜0.01）. One case in the control group showed mild skin allergy， with no other adverse reactions observed in either group. ConclusionBased on three movements technique of QSM， hot ironing with HF shows better clinical efficacy than external Diclofenac Sodium Gel in the treatment of cold-dampness obstruction type LDH. It can significantly reduce lumbar pain， increase pain pressure threshold， improve clinical symptoms， lumbar function， and lumbar curvature， with good safety.

OBJECTIVE: To investigate the susceptibility of venetoclax-resistant acute myeloid leukemia (AML) cell lines to ferroptosis and to uncover the underlying molecular mechanisms using transcriptomic and metabolomic analysis methods. METHODS: Venetoclax-resistant AML cell lines were constructed using a low-dose concentration escalation method. The sensitivity of cells to chemotherapeutic drugs was detected by CCK-8 assay. The susceptibility of drug-resistant cell lines to ferroptosis was assessed using transcriptomic and metabolomic analysis methods. The expression of cellular GPX4 and SLC7A11 protein was detected by Western blot, and cell death and lipid peroxidation levels were measured by flow cytometry. Depmap database and TCGA cohort were applied to explore the effect of ferroptosis-related genes expression on prognosis. RESULTS: Venetoclax-resistant cell lines exhibited sensitivity to ferroptosis inducers RSL3, APR246, and sorafenib. The ferroptosis inhibitor Fer-1 partially inhibited cell death induced by these inducers. Compared with the parental cells, significant changes in metabolites and gene expression levels related to ferroptosis were observed in the resistant cell lines. In particular, deregulated expression of SLC7A11 and GPX4 may play critical role in ferroptosis susceptibility. Besides, GPX4 was identified as more important for AML cell survival and higher GPX4 expression may predict shortened overall survival, NPM1 mutant and IDH1 R132 mutation positive patients may prone to possess higher GPX4 expression. CONCLUSION Venetoclax-resistant AML cell lines remain susceptible to ferroptosis, higher GPX4 expression maybe a critical marker for poor prognosis. Regulating the expression of ferroptosis-related genes and metabolites may enhance the efficacy of venetoclax and provide new treatment options for AML patients.
Humans ; Ferroptosis ; Leukemia, Myeloid, Acute/metabolism* ; Sulfonamides/pharmacology* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Drug Resistance, Neoplasm ; Metabolomics ; Cell Line, Tumor ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Transcriptome

OBJECTIVES: Stigma is common among community-dwelling patients with schizophrenia and has a profound negative impact on both psychiatric symptoms and quality of life. This study aims to explore the association between stigma and quality of life in this population and to examine the multiple mediating roles of anxiety and depression symptoms. METHODS: The multi-stage stratified cluster random sampling method was used to select the community-dwelling patients with schizophrenics in Chengdu, Sichuan Province, China. The questionnaire included general demographic characteristics, stigma question, the Generalized Anxiety Disorder-7 (GAD-7) scale, the Patient Health Questionnaire-9 (PHQ-9), and the 12-item Short Form Health Survey (SF-12). The SF-12 was used to measure quality of life, including physical health and mental health dimensions. A multiple mediation model was used to analyse the mediating effects of anxiety and depression symptoms together between stigma and quality of life. RESULTS: A total of 1 087 community patients with schizophrenia were included with a mean age of 50.68±12.73 years; 525 (48.30%) were male. Stigma was reported by 543 patients (49.95%). Anxiety symptoms were present in 292 patients (26.86%), and depression symptoms in 407 patients (37.44%). The physical health quality of life score was 72.01 ± 20.99, and the mental health quality of life score was 71.68 ± 19.38. Multiple mediation analysis showed that stigma directly affected quality of life, and also indirectly affected quality of life through anxiety and depression symptoms. Anxiety and depression jointly mediated 42.26% of the total effect of stigma on physical health quality of life and 47.51% on mental health quality of life. CONCLUSIONS Reducing stigma and preventing anxiety and depression symptoms in community-dwelling patients with schizophrenia can effectively improve their quality of life and support reintegration into society.
Humans ; Quality of Life ; Male ; Depression/psychology* ; Middle Aged ; Social Stigma ; Schizophrenia ; Female ; Anxiety/psychology* ; China ; Surveys and Questionnaires ; Adult ; Schizophrenic Psychology ; Independent Living ; Aged

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Selenoproteins, as the active form of selenium, play an important role in various physiological and pathological processes, such as anti-oxidation, anti-tumor, immune response, metabolic regulation, reproduction and aging. Although the expression level of selenoproteins in adipose tissue is significantly influenced by dietary selenium intake, it is closely related to the homeostasis of adipose tissue. In this review, we summarized the role of selenoproteins in the physiological function of adipose tissue and the pathogenesis of obesity in recent years, in order to provide a rationale for developing potential therapeutic agents for the treatment of obesity and related metabolic diseases.
Selenoproteins/metabolism* ; Adipose Tissue/physiology* ; Obesity/metabolism* ; Humans ; Animals ; Selenium

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

OBJECTIVE: EPF3 is a fibrinolysin monomer isolated and purified from Pheretima vulgaris Chen, an earthworm used in traditional Chinese medicine as Dilong for treating blood stasis syndrome. Its composition, anticoagulant and fibrinolytic activities, and relevant mechanisms have been confirmed through in vitro experiments. However, whether it has antithrombotic effects in vivo and can be absorbed by the gastrointestinal tract is unknown. This study evaluates the antithrombotic effect in zebrafish and investigates the gastrointestinal stability and intestinal absorption mechanism of this protein in vitro. METHODS: The antithrombotic effect of EPF3 in vivo was verified using the zebrafish thrombus model induced by arachidonic acid and FeCl₃. Then, the protein bands of EPF3 incubated with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and homogenate of Caco-2 cells (HC2C) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to evaluate its gastrointestinal stability. Finally, the transport behavior and absorption mechanism of EPF3 were studied using Caco-2 cell monolayer. RESULTS: EPF3 could significantly enhance the returned blood volume and blood flow velocity in zebrafish with platelet aggregation thrombus induced by arachidonic acid. It could also prolong the formation time of tail artery thrombus and increase the blood flow velocity in zebrafish with vessel injury thrombus induced by FeCl₃. EPF3 was stable in SIF and HC2C and unstable in SGF. The permeability of EPF3 in Caco-2 monolayer was time-dependent and concentration-dependent. The efflux ratio was less than 1.2 during transport, and the transport behavior was not affected by inhibitors. EPF3 could reversibly reduce the expression of tight junction-related proteins, including zonula occludens-1, occludin, and claudin-1 in Caco-2 cells. CONCLUSION EPF3 could play a thrombolytic and antithrombotic role in zebrafish. It could be transported and absorbed into the intestine through cellular bypass pathway by opening the intestinal epithelium tight junction. This study provides a scientific explanation for the antithrombotic effect of earthworm and provides a basis for the feasibility of subsequent development of EPF3 as an antithrombotic enteric-soluble preparation. Please cite this article as: Zhong WL, Yang JQ, Liu H, Wu YL, Shen HJ, Li PY, Du SY. Antithrombotic effect in zebrafish of a fibrinolytic protein EPF3 from Dilong (Pheretima vulgaris Chen) and its transport mechanism in Caco-2 monolayer through cell bypass pathway. J Integr Med. 2025; 23(4): 415-428.
Animals ; Zebrafish ; Humans ; Caco-2 Cells ; Fibrinolytic Agents/pharmacology* ; Thrombosis/drug therapy* ; Intestinal Absorption

Aim To investigate the expression of al-pha-enolase 1(ENO1)in FLT3-mutated acute myeloid leukemia(AML)and its impact on prognosis,as well as to assess the influence of ENO1 on the antitumor effects of FLT3 inhibitors.Methods Data from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed to compare the expression differences of ENO1 in various tumors and normal tissues.ENO1 knockdown cells were con-structed using the AML cell line MOLM13.The impact of ENO1 on AML cell proliferation,apoptosis,and drug sensitivity was evaluated through CCK-8 assays,flow cytometry,drug synergy experiments,transcriptome se-quencing,and lipid peroxide and reactive oxygen spe-cies(ROS)levels were detected.Results The ex-pression level of ENO1 was significantly elevated in FLT3 internal tandem duplication mutation(FLT3-ITD)positive AML patients and was associated with poor prognosis.Knockdown of ENO1 significantly in-hibited AML cell proliferation and induced apoptosis.Inhibition of ENO1 significantly increased the chemo-sensitivity of AML cells to FLT3 inhibitors.Transcrip-tome sequencing analysis revealed differential expres-sion of genes in the NADPH oxidase-related pathway following ENO1 knockdown,and a positive correlation between ENO1 and glutathione peroxidase 4(GPX4)expression.Inhibition of ENO1 significantly increased the levels of lipid peroxides and ROS induced by FLT3 inhibitors.Conclusions High expression of ENO1 is significantly associated with poor prognosis in FLT3(+)AML.Inhibition of ENO1 can enhance the anti-tumor effects of FLT3 inhibitors by regulating the an-tioxidant defense capacity of AML cells,providing a new target and therapeutic strategy for the treatment of FLT3/ITD(+)AML.

Aim To investigate the expression of al-pha-enolase 1(ENO1)in FLT3-mutated acute myeloid leukemia(AML)and its impact on prognosis,as well as to assess the influence of ENO1 on the antitumor effects of FLT3 inhibitors.Methods Data from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases were analyzed to compare the expression differences of ENO1 in various tumors and normal tissues.ENO1 knockdown cells were con-structed using the AML cell line MOLM13.The impact of ENO1 on AML cell proliferation,apoptosis,and drug sensitivity was evaluated through CCK-8 assays,flow cytometry,drug synergy experiments,transcriptome se-quencing,and lipid peroxide and reactive oxygen spe-cies(ROS)levels were detected.Results The ex-pression level of ENO1 was significantly elevated in FLT3 internal tandem duplication mutation(FLT3-ITD)positive AML patients and was associated with poor prognosis.Knockdown of ENO1 significantly in-hibited AML cell proliferation and induced apoptosis.Inhibition of ENO1 significantly increased the chemo-sensitivity of AML cells to FLT3 inhibitors.Transcrip-tome sequencing analysis revealed differential expres-sion of genes in the NADPH oxidase-related pathway following ENO1 knockdown,and a positive correlation between ENO1 and glutathione peroxidase 4(GPX4)expression.Inhibition of ENO1 significantly increased the levels of lipid peroxides and ROS induced by FLT3 inhibitors.Conclusions High expression of ENO1 is significantly associated with poor prognosis in FLT3(+)AML.Inhibition of ENO1 can enhance the anti-tumor effects of FLT3 inhibitors by regulating the an-tioxidant defense capacity of AML cells,providing a new target and therapeutic strategy for the treatment of FLT3/ITD(+)AML.

The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.