ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.

Objective To explore the effect of management model of clinical pharmacists participating in multidisciplinary collaborative diagnosis and treatment(MDT)for new anti-tumor drugs in the national medical insurance drug negotiation(hereinafter referred to as"national negotiation"),including efficacy,safe-ty,economy and rationality.Methods The medical records of 326 cases using novel anti-tumor drugs by na-tional negotiation and conforming to the including and excluding standards in this hospital from July 2018 to June 2023 were retrospectively analyzed.The patients were divided into the MDT group(n=122)and non-MDT group(n=204).The patients diagnosed as non-small cell lung cancer(NSCLC)in the two groups were extracted and defined as the MDT-NSCLC subgroup(n=41)and non-MDT-NSCLC subgroup(n=77).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR)and the indexes such as survival quality and medical quality control were compared between the groups.Results The median PFS in the two groups was 12.7 months and 8.0 months,the median OS was 75.2 months and 56.3 months,DCR was 96.72％and 81.86％respectively,and the differences were statistically significant(P＜0.05).The COX multivariate regression analysis indicated that the HR value of clinical pharmacists participating in MDT was higher than the other influencing factors.The median PFS time in the MDT-NSCLC subgroup and non-MDT-NSCLC subgroup was 10.5 months and 6.7 months,DCR was 97.30％and 75.64％respectively,and the differences were statistically significant(P＜0.05),the median OS time was 55.1 months and 40.3 months respectively,and the difference was statistically significant(P＞0.05).The COX multivariate regression anal-ysis indicated that the HR value with clinical pharmacists participating in MDT was higher than the other in-fluencing factors;The adverse reaction occurrence rate in the MDT group and non-MDT group was 45.9％and 58.3％respectively,and the difference was statistically significant(P＜0.05).The KPS score after treatment in the MDT group was higher than that in the non-MDT group,and the difference was statistically significant;in the aspect of medical quality control,the average drug proportion in the MDT group and non-MDT group was 63.93％and 64.54％respectively,the rational drug rate of comments on prescription was 98.36％and 88.73％respectively,the patient satisfaction average value was 90.69 points and 87.36 points respectively and the differences were statistically significant(P＜0.05).Conclusion Clinical pharmacists participating in MDT related to novel anti-tumor drugs by national negotiation is beneficial to improve the therapeutic effects,living quality and patient satisfaction,also benefit to management and control of off-label drug use and medical quality control indexes.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

The effect of Huanglian Jiedu Decoction on the intestinal flora of type 2 diabetes mellitus(T2DM) was investigated using 16S rRNA sequencing technology. Sixty rats were randomly divided into a normal group(10 rats) and a modeling group(50 rats). After one week of adaptive feeding, a high-fat diet + streptozotocin was given for modeling, and fasting blood glucose >16.7 mmol·L~(-1) was considered a sign of successful modeling. The modeling group was randomly divided into the model group, high-, medium-, and low-dose groups of Huanglian Jiedu Decoction, and metformin group. After seven days of intragastric treatment, the feces, colon, and pancreatic tissue of each group of rats were collected, and the pathological changes of the colon and pancreatic tissue of each group were observed by hematoxylin-eosin staining. The changes in the intestinal flora structure of each group were observed by the 16S rRNA sequencing method. The results showed that compared with the model group, the high-, medium-, and low-dose of Huanglian Jiedu Decoction reduced fasting blood glucose levels to different degrees and showed no significant changes in body weight. The number of islet cells increased, and intestinal mucosal damage attenuated. Alpha diversity analysis revealed that Huanglian Jiedu Decoction reduced the abundance and diversity of intestinal flora in rats with T2DM; at the phylum level, low-and mediam-dose of Huanglian Jiedu Decoction reduced the abundance of Bacteroidota, Proteobacteria, and Desulfobacterota and increased the abundance of Firmicute and Bacteroidota/Firmicutes, while the high-dose of Huanglian Jiedu Decoction increased the relative abundance of Proteobacteria and Bacteroidota/Firmicutes ratio, and decreaseal the relative; abundance of Firmicute; at the genus level, Huanglian Jiedu Decoction increased the relative abundance of Allobaculum, Blautia, and Lactobacillus; LEfse analysis revealed that the biomarker of low-and medium-dose groups of Huanglian Jiedu Decoction was Lactobacillus, and the structure of the intestinal flora of the low-dose group of Huanglian Jiedu Decoction was highly similar to that of the metformin group. PICRUSt2 function prediction revealed that Huanglian Jiedu Decoction mainly affected carbohydrate and amino acid metabolic pathways. It suggested that Huanglian Jiedu Decoction could reduce fasting blood glucose and increase the number of islet cells in rats with T2DM, and its mechanism of action may be related to increasing the abundance of short-chain fatty acid-producing strains and Lactobacillus and affecting carbohydrate and amino acid metabolic pathways.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Diabetes Mellitus, Type 2/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Bacteria/drug effects* ; Blood Glucose/metabolism*

Cervi Cornu Pantotrichum is a precious animal-derived Chinese medicinal material, while there are often adulterants derived from animals not specified in the Chinese Pharmacopeia in the market, which disturbs the safety of medication. This study was conducted with the aim of strengthening the quality control of Cervi Cornu Pantotrichum and standardizing the medication. To achieve digital identification of Cervi Cornu Pantotrichum from different sources, a digital identification model was constructed based on ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS~E) combined with an adaptive boosting algorithm(Adaboost). The young furred antlers of sika deer, red deer, elk, and reindeer were processed and then subjected to polypeptide analysis by UHPLC-QTOF-MS~E. Then, the mass spectral data reflecting the polypeptide information were obtained by digital quantification. Next, the key data were obtained by feature screening based on Gini index, and the digital identification model was constructed by Adaboost. The model was evaluated based on the recall rate, F_1 composite score, and accuracy. Finally, the results of identification based on the constructed digital identification model were validated. The results showed that when the Gini index was used to screen the data of top 100 characteristic polypeptides, the digital identification model based on Adaboost had the best performance, with the recall rate, F_1 composite score, and accuracy not less than 0.953. The validation analysis showed that the accuracy of the identification of the 10 batches of samples was as high as 100.0%. Therefore, based on UHPLC-QTOF-MS~E and Adaboost algorithm, the digital identification of Cervi Cornu Pantotrichum can be realized efficiently and accurately, which can provide reference for the quality control and original animal identification of Cervi Cornu Pantotrichum.
Animals ; Algorithms ; Antlers/chemistry* ; Boosting Machine Learning Algorithms ; Chromatography, High Pressure Liquid/methods* ; Deer ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Quality Control ; Reindeer ; Tandem Mass Spectrometry/methods* ; Tissue Extracts/analysis*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aims to investigate the in vitro mechanisms underlying the beneficial effects of puerarin on hepatic insulin resistance(IR) based on the carbohydrate response element-binding protein(ChREBP)/peroxisome proliferator-activated receptor(PPAR)α/PPARγ axis involved in glucose and lipid metabolism. An IR-HepG2 cell model was established by treating cells with dexamethasone for 48 h, and the cells were then treated with 10, 20, and 40 μmol·L~(-1) puerarin for 24 h. Glucose levels and output in the extracellular fluid were measured by the glucose oxidase method, while cell viability was assessed by the cell counting kit-8(CCK-8) assay. The adenosine triphosphate(ATP) content and glycogen synthesis were evaluated through chemiluminescence and periodic acid-Schiff staining, respectively. Western blot was employed to quantify the protein levels of forkhead box protein O1(FoxO1), phosphorylated forkhead box protein O1 [p-FoxO1(Ser256)], glucagon, phosphofructokinase, liver type(PFKL), pyruvate kinase L-R(PKLR), pyruvate dehydrogenase complex 1(PDHA1), insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase p85(PI3KR1), phosphorylated protein kinase B [p-Akt(Thr308)], glycogen synthase(GYS), glycogen phosphorylase, liver type(PYGL), adiponectin(ADPN), ChREBP, PPARα, and PPARγ. Additionally, the protein levels of acetyl-CoA carboxylase 1(ACC1), phosphorylated ATP citrate lyase [p-ACLY(Ser455)], sterol regulatory element binding protein 1c(SREBP-1c), peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α), carnitine palmitoyltransferase 1α(CPT1α), and glucagon receptor(GCGR) were also determined. Immunofluorescence was employed to visualize the expression and nuclear location of ChREBP/PPARα/PPARγ. Furthermore, quantitative PCR with the antagonists GW6471 and GW9662 was employed to assess Pparα, Pparγ, and Chrebp. The findings indicated that puerarin effectively reduced both the glucose level and glucose output in the extracellular fluid of IR-HepG2 cells without obvious effect on the cell viability, and it increased intracellular glycogen and ATP levels. Puerarin down-regulated the protein levels of FoxO1 and glucagon while up-regulating the protein levels of p-FoxO1(Ser256), PFKL, PKLR, PDHA1, IRS2, PI3KR1, p-Akt(Thr308), GYS, PYGL, ADPN, ACC1, SREBP-1c, p-ACLY(Ser455), PGC1α, CPT1α, and GCGR in IR-HepG2 cells. Furthermore, puerarin up-regulated both the mRNA and protein levels of ChREBP, PPARα, and PPARγ and promoted the translocation into the nucleus. GW6471 was observed to down-regulate the expression of Pparα while up-regulating the expression of Chrebp and Pparγ. GW9662 down-regulated the expression of Pparγ while up-regulating the expression of Pparα, with no significant effect on Chrebp. In summary, puerarin activated the hepatic ChREBP/PPARα/PPARγ axis, thereby coordinating the glucose and lipid metabolism, promoting the conversion of glucose to lipids to exert the blood glucose-lowering effect.
Isoflavones/pharmacology* ; Humans ; PPAR gamma/genetics* ; Hep G2 Cells ; Glucose/metabolism* ; Lipid Metabolism/drug effects* ; PPAR alpha/genetics* ; Liver/drug effects* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Insulin Resistance