Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Opioid analgesics are currently known as the best analgesics. However， toxicity and side effects such as constipation， tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology， researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics， which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation，“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced， and the latest research progress of representative drugs is briefly reviewed. Among them， the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists， Cebranopadol is a typical “one drug-multiple targets” analgesic， and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.

AIM:To explore the mechanism by which Qingshen granules(QSG)intervene in the microRNA-4516(miR-4516)targeted regulation of the SIAH3/PINK1 axis,enhancing mitophagy and inhibiting renal fibrosis.METHODS:Male SD rats were randomly divided into three groups:control,model,and QSG groups.The QSG aqueous solution was administered via gavage once daily,4 mL each time,for 8 consecutive weeks.Blood creatinine levels were measured in each group.Hematoxylin-eosin(HE)and Masson staining were utilized to assess the degree of renal patholog-ical damage.Western blot analysis was performed to determine the expression levels of β-actin,PINK1,Parkin,SIAH3,VDAC1,Mfn1,Mfn2,OPA1,LC3B,and P62 proteins in renal tissue.RT-qPCR was used to detect the mRNA expres-sion level of SIAH3 in rat kidney tissue,and transmission electron microscopy was employed to observe mitochondrial dam-age in renal tissue.QSG-containing serum and transforming growth factor-β1(TGF-β1)were used to induce an HK-2 cell fibrosis model.The cells were divided into the following groups:normal cell(NC)group,model cell(MC)group,MC+miR-4516 mimics group,MC+miR-4516 NC+QSG group,MC+miR-4516 mimics+QSG group,and MC+QSG group.Cell activity in each group was detected using the CCK-8 method,and Western blot analysis was performed to determine E-cad-herin and α-SMA protein expression levels.The regulation of SIAH3 by miR-4516 was verified using a dual luciferase re-porter assay.RT-qPCR was used to detect the mRNA expression of miR-4516,SIAH3 mRNA,and PINK1.RESULTS:The results indicated that QSG intervention reduced fibrosis in rat renal tissue and HK-2 cells,decreased SIAH3 mRNA expression,increased PINK1 expression,and activated mitophagy in renal tissue.In vitro results confirmed that QSG can elevate miR-4516 expression,inhibit SIAH3 mRNA expression,promote PINK1 expression in HK-2 cells,and reduce the expression of the fibrosis marker protein α-SMA.CONCLUSION:In summary,this study preliminarily clarified the mechanism by which QSG intervention targets miR-4516 to regulate the SIAH3/PINK1 axis,thereby enhancing mitophagy and inhibiting renal fibrosis.

This article summarized Professor Zhu Renkang's experience in treating chronic eczema with Ziyin Chushi Decoction.Professor Zhu Renkang believes that eczema's onset is inseparable from pathogenic dampness.Pathogenic dampness runs through all stages of the disease.Stage of attack is dominated by excessive pathogen.Pathogenic wind attacks the exterior,while the muscular interstices is not dense,which makes nutritive yin leak out and stagnate as pathogenic dampness,then wind and dampness combined with each other.Chronic stage is dominated by yin deficiency.Long-term illness damages healthy qi,and pathogenic dampness conceals in the body,which makes deficiency of nutritive yin inside and dryness outside.Professor Zhu Renkang focuses on the characteristics of chronic eczema characterized by deficiency of yin and retention of dampness pathogens.He establishes Ziyin Chushi Decoction,and emphasizes that nutritive yin and pathogenic dampness have the same origin but different paths and can exist simultaneously.The combined utilization of nourishing yin and eliminating dampness can restore yin without helping dampness,remove dampness without harming yin,which have achieved satisfactory efficacy.

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Cerebral small vessel disease (CSVD) is a series of diseases originating from pathological changes in cerebral microvessels, with a high prevalence in the population of advanced age. CSVD may significantly increase the risk of various neurological disorders, including cognitive impairment and stroke. With the development and application of advanced imaging techniques such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), there has been a deeper understanding of the brain function and microstructural changes in patients with CSVD. This article reviews some new indicators and analysis methods of fMRI and DTI in CSVD research, and elaborates on their correlation with patient clinical manifestations.

Objective The aim of this study is to combine Raman spectroscopy and machine learning techniques to distinguish subgin-gival plaques among three groups of subjects,including patients with chronic periodontitis(CP)and type 2 diabetes mellitus(T2DM),patients with CP alone,and healthy controls.Methods The Raman spectra of the subgingival plaques from 20 patients with CP and T2DM(group A),23 patients with CP alone(group B),and 23 healthy controls(group C)were obtained using a portable Raman spec-trometer.Eight common machine learning algorithms were applied to build models to distinguish the Raman spectra of the three types of subgingival plaques.Results The model identified as optimal for distinguishing the three types of subgingival plaques was linear discri-minant analysis(LDA).The optimal model to distinguish groups A and B is LDA,groups A and C is extra trees(ET),and groups B and C group is LDA.Conclusion The proposed classification model based on Raman spectroscopy and machine learning algorithms can dis-tinguish subgingival plaques among patients with CP and T2DM,with CP alone,and healthy controls.This technique can be used in future clinical practice as a screening or diagnostic tool.