ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

Objective:To analyze the preferences of medical staff in TCM hospitals in Beijing regarding the achievements transformation of hospital traditional Chinese medicine preparations,and to provide a reference for formulating incentive policies.Methods:233 medical staff from five TCM hospitals in Beijing were taken as the research objects,and surveyed with a questionnaire designed based on the discrete choice experiment(DCE).Mixed logit models and latent class models were then used to analyze their transformation preferences.Results:The mixed Logit model revealed that seven key attributes significantly influenced medical staff's preferences for the achievements transformation of traditional Chinese medicine preparations(P<0.05).Latent class analysis identified three distinct preference groups among respondents:an organization-dependent group(27.0%),a pro-transformation group(61.4%),and a conservative group(11.6%).Conclusions:Medical Staff preferred transformation conditions that increased monthly income;utilized"human use+re-experimentation";involved the hospital's achievements transformation department as the entity;were funded by the hospital;offered a 70%profit share;enabled promotion three years earlier,and assigned patents to the hospital.The study recommends implementing diverse incentive measures and developing differentiated strategies tailored to the distinct Medical Staff categories to facilitate the transformation of hospital traditional Chinese medicine preparations into new drugs.

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.

Cardiovascular disease is one of the most common causes of death in the world,and related western drugs usually have obvious side effects.Traditional Chinese medicine,characterized by its multi-component and multi-target,has unique advantage in the prevention and treatment of cardiovascular diseases.Cornus Officinal is a histor-ically used plants with medicinal and edible properties.Ancient books and modern literatures have shown that Cor-nus Officinal has the potential to prevent and treat cardiovascular diseases.With the in-depth study of the chemical composition and pharmacological effect of Cornus Officinal,its pharmacodynamic substances and mechanism in the prevention and treatment of cardiovascular diseases are gradually clear.This article reviews the pathways and targets of Cornus Officinal in the prevention and treatment of cardiovascular diseases in recent years,and summarizes its potential effective components,in order to provide theoretical support for the clinical application and traditional Chinese medicine development.

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.

Cardiovascular disease is one of the most common causes of death in the world,and related western drugs usually have obvious side effects.Traditional Chinese medicine,characterized by its multi-component and multi-target,has unique advantage in the prevention and treatment of cardiovascular diseases.Cornus Officinal is a histor-ically used plants with medicinal and edible properties.Ancient books and modern literatures have shown that Cor-nus Officinal has the potential to prevent and treat cardiovascular diseases.With the in-depth study of the chemical composition and pharmacological effect of Cornus Officinal,its pharmacodynamic substances and mechanism in the prevention and treatment of cardiovascular diseases are gradually clear.This article reviews the pathways and targets of Cornus Officinal in the prevention and treatment of cardiovascular diseases in recent years,and summarizes its potential effective components,in order to provide theoretical support for the clinical application and traditional Chinese medicine development.

Objective:To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria (PNH) and evaluate their association with clinical manifestations.Methods:This study enrolled patients with PNH, who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023. The clinical information of participants was retrospectively recorded, and peripheral blood samples were collected. Gender- and age-matched normal controls (NC) were recruited accordingly. C5b-9, C3, C4b, and factor B (FB) deposition levels on peripheral red blood cells, white blood cells, and platelets were detected with flow cytometry. The correlation between complement deposition levels and clinical symptoms was analyzed.Results:This study involved 73 patients with PNH, including 42 (57.5%) males, with a median age of 36 (range: 14-76) years. 16 matched NC were collected. Among patients with PNH, 36 (49.3%) had classical PNH and 37 (50.7%) had aplastic anemia-PNH syndrome. Thromboembolic events (TEE) occurred in 18 (24.7%) patients. The median HGB, absolute reticulocyte count (Ret), and lactate dehydrogenase of PNH patients were 76 (37-116) g/L, 181.0 (45.9-495.8) ×10 9/L, and 1 875 (377 - 5 509) U/L, respectively. The median number of Flaer-negative white blood cells was 94.0% (13.0% - 99.9%) ; the median CD59 negative red blood cells was 46.7% (9.0% - 93.0%). The deposition of C5b-9, C3, C4b, and FB on red blood cells, white blood cells, and platelets in patients with PNH was significantly higher than that in NC (all P<0.05). C5b-9 deposition level was significantly higher than that of C3, C4b, and FB on all three blood cell lineages in PNH patients (all P<0.01). The deposition of all complement fragments on red blood cells was significantly lower than that on white blood cells and platelets (all P<0.01). C5b-9 deposition on red blood cells was positively correlated with Ret in PNH patients ( P=0.005). C3 ( P=0.001) and C4b ( P=0.017) deposition levels on white blood cells and C3 deposition on platelets ( P=0.002) in patients with TEE history were lower than those without. Conclusions:C5b-9, C3, C4b, and FB deposition levels on all three blood cells in patients with PNH were higher than NC. Increased C5b-9 on red blood cells may indicate active hemolysis. Reduced C3 and C4b levels on white blood cells and low C3 deposition on platelets may indicate TEE risk.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective To investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.