ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Objective: To explore the distribution of traditional Chinese medicine (TCM) syndromes in children with hepatolenticular degeneration (Wilson disease, WD) based on factor analysis and cluster analysis. Methods: From November 2018 to November 2023, general information (gender, age of admission, age of onset, course of disease, clinical staging, Western medicine clinical symptoms, and family history) and TCM four-examination informations (symptoms and signs) were retrospectively collected from 757 cases of children with WD at the First Affiliated Hospital of Anhui University of Chinese Medicine, and factor analysis and cluster analysis were used to investigate TCM syndromes in children with WD. Results: A total of 757 children with WD were included, of which 483 were male and 274 were female; the median age at admission was 12.58 years, the median age at onset was 8.33 years, and the median course of disease was 24.37 months; clinical typing result indicated 506 cases of hepatic type, 133 cases of brain type, 99 cases of mixed-type, and 19 cases of other type; 36.46% of the children had no clinical symptoms (elevated aminotransferases or abnormalities in copper biochemistry); a total of 177 cases had a definite family history, and 10 cases had a suspected family history. Forty-three TCM four-examination information were obtained, with the top 10 in descending order being feeling listless and weak, brown urine, slow action, inappetence, dim complexion, slurred speech, angular salivation, body weight loss, hand and foot tremors, and abdominal fullness. In children with WD, the syndrome element of disease location was primarily characterized by the liver, involving the spleen and kidney, and the syndrome elements of disease nature were characterized by dampness, heat, and yin deficiency. Based on factor analysis and cluster analysis, five TCM syndromes were derived, which were, in order, syndrome of dampness-heat accumulation (265 cases, 35.01%), syndrome of yin deficiency of the liver and kidney (202 cases, 26.68%), syndrome of liver hyperactivity with spleen deficiency (185 cases, 24.44%), syndrome of qi and blood deficiency (79 cases, 10.44%), and syndrome of yang deficiency of the spleen and kidney (26 cases, 3.43%). Conclusion The TCM syndromes of children with WD were primarily syndromes of dampness-heat accumulation, yin deficiency of the liver and kidney, and liver hyperactivity with spleen deficiency. The liver was the main disease location, and the disease nature was characterized by deficiency in origin and excess in superficiality, excess and deficiency mixed. These findings suggest that treating children with WD should be based on the liver while also considering the spleen and kidney.

Objective To investigate the distribution and antibiotic resistance of clinical isolates in the Traditional Chinese Medicine Hospital of Xinjiang Medical University.Methods Bacterial strains were collected from January 1,2020,to December 31,2023,and tested for antimicrobial susceptibility using automated systems and disk diffusion methods.The results were interpreted according to the breakpoints recommended in the CLSI M100.Results Over the four-year period,22 121 bacterial strains were analyzed,including Gram-positive bacteria(24.1％,5 338/22 121)and Gram-negative bacteria(75.9％,16 783/22 121).The prevalence of methicillin-resistant S.aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococcus(MRCNS)was 26.4％and 68.9％,respectively.MRSA and MRCNS strains showed higher resistance rates to most antimicrobial agents compared to methicillin-susceptible strains(MSSA and MSCNS).No Staphylococcus strains were found resistant to linezolid or vancomycin.E.faecium showed higher resistance rates to most of the antimicrobial agents tested than E.faecalis.A few vancomycin-resistant strains were identified in E.faecium and limited number of linezolid-resistant strains were identified in E.faecalis.All S.pneumoniae isolates were isolated from specimens other than cerebrospinal fluid.The prevalence of penicillin-resistant S.pneumoniae(PRSP)was 9.4％.Overall,13.2％of Klebsiella isolates were resistant to imipenem and 13.1％to meropenem,while the prevalence of carbapenem-resistant strains was less than 10％in Escherichia coli or other genera of Enterobacterales.As for non-fermenting Gram-negative bacteria,P.aeruginosa was largely susceptible to most antimicrobial agents.Overall,11.8％and 10.9％of P.aeruginosa strains were resistant rates to imipenem and meropenem,respectively.However,47.1％of Acinetobacter strains were resistant to imipenem and 47.9％to meropenem,while 14.9％to 53.2％of the strains were resistant to other antimicrobial agents tested.Conclusions The clinical strains isolated in the Traditional Chinese Medicine Hospital of Xinjiang Medical University were predominantly Gram-negative bacteria.The prevalence of carbapenem-resistant strains in Klebsiella spp.was higher than that in other species of Enterobacterales.Acinetobacter spp.showed high resistance rate to carbapenems.The prevalence of methicillin-resistant strains was high in Staphylococcus.Vancomycin-resistant and linezolid-resistant strains were identified in Enterococcus spp.Infection prevention and control and stewardship of antimicrobial agents should be strengthened to contain the emergence and spread of resistant bacteria.

Objective By observing the clinical efficacy of Zhinao capsule in the treatment of Parkinson's disease with mild cognitive impairment(PD-MCI)patients,we also explored the potential mechanism using network pharmacology and molecular docking technology,with the aim of providing a new idea for the treatment of PD-MCI with traditional Chinese medicine.Methods Random number table method was applied to divide the control group and test group into 35 cases each.Parkinson's disease basic treatment plan was used in the control group,and Zhinao capsule was added in the test group.The observation course was determined to be 8 weeks.The Montreal Cognitive Assessment(MoCA)score,MDS-Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅰ,Ⅱ and Ⅲ,PD Traditional Chinese Medicine(PD-TCM),and safety-related indexes were completed before treatment and at the end of the 8th week of treatment.The network pharmacology method was used to obtain the targets related to Zhinao capsules and PD-MCI.Constructed and analyzed the"drug-component-target"network.Analysis of"drug-disease"intersecting targets and enrichment of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was obtained using R language.Protein-protein interaction(PPI)networks were constructed using Cytoscape 3.9.1.Finally,molecular docking was conducted.Results The MoCA score of the test group was remarkably greater than that of the control group after treatment(P<0.05);and the TCM syndrome score were noticeably below that of the control group(P<0.05).The test group showed a notable increase in the mean value of MoCA scale scores,and a clear decrease in the MDS-UPDRS Ⅰand PD-TCM before and after treatment(P<0.05).The MDS-UPDRS Ⅱ and Ⅲ scale scores of the test and control groups decreased to different degrees after treatment,but there was no significant difference(P>0.05).Zhinao capsules for PD-MCI treatment has calycosin,quercetin,kaempferol,etc.as core active ingredients,and TNF,IL-1β,IL-6,etc.as core targets.Molecular docking results also showed better binding of the core target to the active ingredient.Zhinao capsules regulates the expression of PPAR,cGMP-PKG,Oxytocin and other signaling pathway-related genes.Conclusion The Zhinao capsules can improve the cognitive function of PD-MCI patients,and the mechanism may be related to the fact that the components such as calycosin,quercetin,and kaempferol act on the targets such as TNF,IL-1β,and IL-6,and mediate the signaling pathways such as PPAR,cGMP-PKG,and Oxytocin.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Aim To predict the mechanism of action of ginsenoside Rg1(G-Rg1)paired with hirudin in the treatment of myocardial fibrosis in acute myocardial in-farction(AMI)based on the network pharmacology ap-proach,and to validate it by in vivo and in vitro experi-ments.Methods The corresponding targets of G-Rg1 and Hirudin were collected using SwissTargetPredic-tion,TargetNet,ETCM and ChEMBL databases,and the targets related to AMI and myocardial fibrosis were collected using GeneCards,OMIM and DisGeNET da-tabases.The drug-disease intersection targets were subjected to protein-protein interaction network(PPI)network analysis,gene ontology(GO)functional en-richment analysis and kyoto encyclopedia of genomes(KEGG)pathway enrichment analysis.Key targets and pathways were validated using an AMI mouse mod-el induced by ligation of the anterior descending branch of the left coronary artery in mice versus a hypoxia-in-duced injury model of human cardiac microvascular en-dothelial cells(HCMECs).Results G-Rg1 paired with hirudin had 229 drug targets,816 AMI and myo-cardial fibrosis disease targets,and 65 intersecting tar-gets.PPI analysis showed that tumor necrosis factor(TNF),interleukin-1[3(IL-1 β),transforming growth factor beta-1(TGF-β1),nuclear factor kappa-B(NF-κB),and interleukin-6(IL-6)might be the core tar-gets of G-Rg1 paired with Hirudin in the treatment of post-MI myocardial fibrosis;KEGG was enriched for a total of 141 pathways involving endocrine and metabo-lism,inflammation,and immunity,mainly TNF signa-ling pathway,PI3K/Akt signaling pathway and TGF-βsignaling pathway.In vivo experiments confirmed that G-Rg1 paired with hirudin attenuated myocardial fibro-sis after AMI in mice,and down-regulated the expres-sion of TNF-α,IL-1β,NF-κB,TGF-β1,and Smad2/3 proteins in myocardial tissues.In vitro experiments confirmed that G-Rg1 paired with Hirudin inhibited cellular NF-κB/TGF-β1 pathway,reduced hypoxia-in-duced cellular TNF-α and IL-1β expression,and su-perimposed NF-κB inhibitor significantly reduced IL-1 β expression and attenuated cellular inflammatory re-sponse.Conclusions G-Rg1 with Hirudin treats post-MI myocardial fibrosis by regulating TNF-α,IL-1 β and other targets and NF-KB/TGF-β1 pathway,reflecting its multi-pathway and multi-target action characteris-tics,and providing a pharmacological basis for the treatment of post-MI myocardial fibrosis with G-Rg1 with Hirudin.

Objective By observing the clinical efficacy of Zhinao capsule in the treatment of Parkinson's disease with mild cognitive impairment(PD-MCI)patients,we also explored the potential mechanism using network pharmacology and molecular docking technology,with the aim of providing a new idea for the treatment of PD-MCI with traditional Chinese medicine.Methods Random number table method was applied to divide the control group and test group into 35 cases each.Parkinson's disease basic treatment plan was used in the control group,and Zhinao capsule was added in the test group.The observation course was determined to be 8 weeks.The Montreal Cognitive Assessment(MoCA)score,MDS-Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅰ,Ⅱ and Ⅲ,PD Traditional Chinese Medicine(PD-TCM),and safety-related indexes were completed before treatment and at the end of the 8th week of treatment.The network pharmacology method was used to obtain the targets related to Zhinao capsules and PD-MCI.Constructed and analyzed the"drug-component-target"network.Analysis of"drug-disease"intersecting targets and enrichment of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was obtained using R language.Protein-protein interaction(PPI)networks were constructed using Cytoscape 3.9.1.Finally,molecular docking was conducted.Results The MoCA score of the test group was remarkably greater than that of the control group after treatment(P<0.05);and the TCM syndrome score were noticeably below that of the control group(P<0.05).The test group showed a notable increase in the mean value of MoCA scale scores,and a clear decrease in the MDS-UPDRS Ⅰand PD-TCM before and after treatment(P<0.05).The MDS-UPDRS Ⅱ and Ⅲ scale scores of the test and control groups decreased to different degrees after treatment,but there was no significant difference(P>0.05).Zhinao capsules for PD-MCI treatment has calycosin,quercetin,kaempferol,etc.as core active ingredients,and TNF,IL-1β,IL-6,etc.as core targets.Molecular docking results also showed better binding of the core target to the active ingredient.Zhinao capsules regulates the expression of PPAR,cGMP-PKG,Oxytocin and other signaling pathway-related genes.Conclusion The Zhinao capsules can improve the cognitive function of PD-MCI patients,and the mechanism may be related to the fact that the components such as calycosin,quercetin,and kaempferol act on the targets such as TNF,IL-1β,and IL-6,and mediate the signaling pathways such as PPAR,cGMP-PKG,and Oxytocin.

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans ; Child ; Hematologic Diseases/therapy* ; Blood Transfusion/standards* ; Practice Guidelines as Topic