ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P0.05）， and compared with the model group， both were significantly increased in the Sini San group （P0.05， P0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P0.05， P0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley （SD） rats were randomly divided into a normal group， model group （M）， Sini San group （MS， 2.5 g·kg^-1）， and fluoxetine group （MF， 2 mg·kg^-1）. Except for the normal group， rats in the other three groups were subjected to chronic unpredictable mild stress （CUMS）. After 8 weeks， the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum corticosterone （CORT）， adrenocorticotropic hormone （ACTH）， corticotropin-releasing factor （CRF）， lipopolysaccharide （LPS）， Zonulin， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， γ-aminobutyric acid （GABA） levels in the hippocampus and prefrontal cortex， and brain-derived neurotrophic factor （BDNF） levels in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy， and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group， the sucrose preference of rats in the model group was significantly reduced （P<0.01）， whereas it was significantly increased in the Sini San group compared with the model group （P<0.05）. Compared with the normal group， hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased （P<0.05）， and compared with the model group， both were significantly increased in the Sini San group （P<0.05， P<0.01）. Compared with the normal group， serum LPS and Zonulin levels in the model group were significantly increased （P<0.05， P<0.01）， and compared with the model group， Zonulin levels in the Sini San group were significantly decreased （P<0.05）. No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group， widened and blurred tight junctions， sparse and shortened microvilli， and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group， which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators， liver function， and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.

[Objective]To deepen the theoretical grasp of"the concept of circular transformation"and apply it to unpack the complex pathogenesis of coronary heart disease(CHD),offering a holistic,unified,and adaptable diagnostic and management framework.[Methods]Through historical review and medical principle analysis,it elucidates"the concept of circular transformation"basics and nuances.Merging this with modern research,it discerns CHD's tangled progression,also refers classic formulas,common drugs and diverse clinical practice to pinpoint effective therapeutic approaches.[Results]"The concept of circular transformation"posits that all phenomena are in cyclic and dynamic flux,with human life exhibiting three cycles:Yin-Yang dynamics,the five elements and Qi movement.This framework can explain CHD pathogeneses as:Yin-Yang imbalance from Yang's failure to disperse and Yin evil obstruction;five elements disharmony due to heart and spleen malnourishment and kidney water overflowing into the heart;and Qi circulation disruption from chaotic ascending-descending and misdirected entry-exit.The treatment strategies include warming Yang Qi,dissipating pathogens,harmonizing Yin-Yang;invigorating the spleen and protecting,the heart warming the kidney,supporting Yang and promoting element interaction;and balancing Qi's movements.This work aims to refine"the concept of circular transformation"and offer systematic,dynamic traditional Chinese medicine(TCM)approaches for CHD diagnosis and treatment.[Conclusion]"The concept of circular transformation"blends concepts of perpetual cycles and evolutionary shifts with traditional Chinese medicine's views on Yin-Yang balance,the five elements'interplay and the movements of Qi.This perspective facilitates sophisticated analysis of CHD's complexity,guiding medication choices and dynamic treatment applications in clinical settings.

[Objective]To explore the pattern of analogical pharmacology and efficacy of"Chinese medicines from covering",which refers to the barks of plants,skins of animals and peels of fruits used as medicines to treat diseases.[Methods]Based on the principle of analogical pharmacology and on the basis of the principle that"Chinese medicines from covering affecting the skin",this paper combines the records in herbal medical classics and clinical medication experience to further analyze the efficacy characteristics of Chinese medicines from covering and summarize the efficacy characteristics of subdivided categories such as fruit peels,bark of trunks,root barks and animal skins.[Results]Chinese medicines from covering have the characteristics of functioning well at entering the lung and large intestine and exerting the effects of relieving cough and diarrhea.This is particularly true for medicines made from fruit peels,such as Pyrus bretschneideri Rehd.peel,Trichosanthes kirilowii Maxim.peel,Exocarpium Citri Grandis and Papaver somniferum L.pericarp.In addition,Morus alba L.root-bark,Fraxinus rhynchophylla Hance bark,Erinaceus europaeus L.skin and Ailanthus altissima(Mill.)Swingle bark also have a preference for entering the lung and large intestine meridians.Chinese medicines from covering have the efficacy characteristic of adepting at nourishing Yin,such as Colla Corii Asini(E jiao),pig skin and Bos taurus domesticus Gmelin hide gelatin,etc.This kind of Chinese medicines from covering generally comes from animal skins.Chinese medicines from covering like Citrus reticulata Blanco pericarp,Pericarpium Citri Reticulatae Viride,Poncirus trifoliata(L.)Raf.fruit,Areca catechu L.peel and Magnolia officinalis Rehd.et Wils.bark are rich in volatile oils and good at regulating Qi and relieving distension.Chinese medicines from covering have the characteristics of being good at entering the lower-Jiao,tonifying the liver and kidney,strengthening the muscles and bones,and consolidating kidney Qi,This is especially true for medicines made from trunk and root barks,such as Phellodendron chinense Schneid.bark,Paeonia suffruticosa Andr.root-bark,Lycium chinense Mill.root-bark,Eleutherococcus gracilistylus W.W.Smith bark and Cinnamomum cassia Presl bark.[Conclusion]In addition to"affecting the skin",Chinese medicines from covering possess various characteristics of efficacy patterns.In the theory of the Five Elements,Chinese medicines from covering pertain to metal.The characteristics of metal Qi,such as its high-rising nature,its functions of ripening,descending and its dryness,are the root causes of the efficacy characteristics of Chinese medicines from covering.These include acting on the skin and the exterior,entering the lungs and large intestine,being rich in colloids and oils,being good at tonifying the liver and kidney,and clearing heat and drying dampness.

[Objective]To deepen the theoretical grasp of"the concept of circular transformation"and apply it to unpack the complex pathogenesis of coronary heart disease(CHD),offering a holistic,unified,and adaptable diagnostic and management framework.[Methods]Through historical review and medical principle analysis,it elucidates"the concept of circular transformation"basics and nuances.Merging this with modern research,it discerns CHD's tangled progression,also refers classic formulas,common drugs and diverse clinical practice to pinpoint effective therapeutic approaches.[Results]"The concept of circular transformation"posits that all phenomena are in cyclic and dynamic flux,with human life exhibiting three cycles:Yin-Yang dynamics,the five elements and Qi movement.This framework can explain CHD pathogeneses as:Yin-Yang imbalance from Yang's failure to disperse and Yin evil obstruction;five elements disharmony due to heart and spleen malnourishment and kidney water overflowing into the heart;and Qi circulation disruption from chaotic ascending-descending and misdirected entry-exit.The treatment strategies include warming Yang Qi,dissipating pathogens,harmonizing Yin-Yang;invigorating the spleen and protecting,the heart warming the kidney,supporting Yang and promoting element interaction;and balancing Qi's movements.This work aims to refine"the concept of circular transformation"and offer systematic,dynamic traditional Chinese medicine(TCM)approaches for CHD diagnosis and treatment.[Conclusion]"The concept of circular transformation"blends concepts of perpetual cycles and evolutionary shifts with traditional Chinese medicine's views on Yin-Yang balance,the five elements'interplay and the movements of Qi.This perspective facilitates sophisticated analysis of CHD's complexity,guiding medication choices and dynamic treatment applications in clinical settings.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

[Objective]To explore the pattern of analogical pharmacology and efficacy of"Chinese medicines from covering",which refers to the barks of plants,skins of animals and peels of fruits used as medicines to treat diseases.[Methods]Based on the principle of analogical pharmacology and on the basis of the principle that"Chinese medicines from covering affecting the skin",this paper combines the records in herbal medical classics and clinical medication experience to further analyze the efficacy characteristics of Chinese medicines from covering and summarize the efficacy characteristics of subdivided categories such as fruit peels,bark of trunks,root barks and animal skins.[Results]Chinese medicines from covering have the characteristics of functioning well at entering the lung and large intestine and exerting the effects of relieving cough and diarrhea.This is particularly true for medicines made from fruit peels,such as Pyrus bretschneideri Rehd.peel,Trichosanthes kirilowii Maxim.peel,Exocarpium Citri Grandis and Papaver somniferum L.pericarp.In addition,Morus alba L.root-bark,Fraxinus rhynchophylla Hance bark,Erinaceus europaeus L.skin and Ailanthus altissima(Mill.)Swingle bark also have a preference for entering the lung and large intestine meridians.Chinese medicines from covering have the efficacy characteristic of adepting at nourishing Yin,such as Colla Corii Asini(E jiao),pig skin and Bos taurus domesticus Gmelin hide gelatin,etc.This kind of Chinese medicines from covering generally comes from animal skins.Chinese medicines from covering like Citrus reticulata Blanco pericarp,Pericarpium Citri Reticulatae Viride,Poncirus trifoliata(L.)Raf.fruit,Areca catechu L.peel and Magnolia officinalis Rehd.et Wils.bark are rich in volatile oils and good at regulating Qi and relieving distension.Chinese medicines from covering have the characteristics of being good at entering the lower-Jiao,tonifying the liver and kidney,strengthening the muscles and bones,and consolidating kidney Qi,This is especially true for medicines made from trunk and root barks,such as Phellodendron chinense Schneid.bark,Paeonia suffruticosa Andr.root-bark,Lycium chinense Mill.root-bark,Eleutherococcus gracilistylus W.W.Smith bark and Cinnamomum cassia Presl bark.[Conclusion]In addition to"affecting the skin",Chinese medicines from covering possess various characteristics of efficacy patterns.In the theory of the Five Elements,Chinese medicines from covering pertain to metal.The characteristics of metal Qi,such as its high-rising nature,its functions of ripening,descending and its dryness,are the root causes of the efficacy characteristics of Chinese medicines from covering.These include acting on the skin and the exterior,entering the lungs and large intestine,being rich in colloids and oils,being good at tonifying the liver and kidney,and clearing heat and drying dampness.

Objective To investigate the characteristics of epilepsy onset based on the theory of five circuits and six qi in traditional Chinese medicine(TCM).Methods A total of 8 389 epilepsy patients from a community-based natural population cohort study from UK Biobank were included.Frequency and constituent ratio analyses were performed to describe the distribution of epilepsy onset in relation to the five circuits and six qi elements,and statistical inferences were made using chi-square tests.Results The analysis revealed statistically significant differences existed in epilepsy onset across different heavenly stems,earthly branches,recombinant yearly circuit,celestial control and terrestrial effect,and dominant qi(all P＜0.05).From the perspective of circuits,the highest incidence occurred in years corresponding to the"Ji"and"Hai"years,while the lowest incidence was observed in"Bing"and"Mao"years.Years dominated by wood circuit and wind manifestations exhibited the highest incidence,whereas years with cold manifestations showed the lowest incidence,suggesting the liver as the primary pathological site in epilepsy.From the perspective of qi,the third dominant qi was most frequently associated with onset.Regarding presiding and subordinate qi,years with taiyin damp earth presiding and taiyang cold water subordinate had the highest incidence,while years with yangming dry metal presiding and shaoyang monarch fire subordinate had the lowest incidence,indicating that cold-damp years and midsummer periods are potential triggers for epilepsy.Conclusion There is a certain regularity in the epilepsy onset correlated with the features of five circuits and six qi,which can guide prevention and clinical diagnosis and treatment of epilepsy.

Objective:To investigate the effects and mechanisms of angiotensin-converting enzyme 2 (ACE2) and Captopril (CAP) on mechanical ventilation-induced lung injury (VILI) in mice.Methods:Seventy-two healthy male BALB/c mice were randomly assigned (using a random number table) into six groups ( n=12 per group): normal control (NC) group, VILI group, ACE2 group, VILI+ACE2 group, CAP group, and VILI+CAP group. One hour prior to mechanical ventilation, the ACE2 and VILI+ACE2 groups were intraperitoneally injected with ACE2 at a dose of 0.1 mg/kg, while the CAP and VILI+CAP groups were intraperitoneally injected with CAP at a dose of 2.5 mg/kg. Following mechanical ventilation, serum samples were collected and enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors [platelet activating factor (PAF), endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2 (PGE2)] and cardiovascular system related indicators [von Willebrand factor (vWF), thrombomodulin (TM), angiotensin (Ang) (1-9), Ang (1-7), prostacyclin I 2 (PGI2)]. Bronchoalveolar lavage fluid (BALF) was gathered, and total protein concentration was determined using BCA method, and sICAM-1 levels were measured by ELISA. Lung tissues were collected and subjected to hematoxylin and eosin staining (HE staining) for the assessment of pathological lung injury and lung injury scoring. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to detect the relative expression levels of ACE2 protein and mRNA, respectively. Statistical analysis was performed using IBM SPSS 20.0 software. Intergroup comparisons were conducted using one-way analysis of variance followed by the least significant difference (LSD) test. Results:No statistically significant differences were observed in the levels of PAF, ET-1, sICAM-1, vWF, TM, Ang(1-9), Ang(1-7), and PGI2 in serum and lung tissues between the ACE2/CAP groups and the NC group (all P>0.05). Compared with the VILI group, the VILI+ACE2 and VILI+CAP groups exhibited significantly decreased serum and lung tissue levels of PAF, ET-1, sICAM-1, and vWF (all P<0.05), while the levels of TM, Ang(1-9), Ang(1-7), and PGI2 were significantly increased (all P<0.05). Pathological lung injury was alleviated, and the lung wet/dry weight ratio was significantly reduced (all P<0.05) in the VILI+ACE2 and VILI+CAP groups. Furthermore, both ACE2 protein and mRNA expression levels were significantly increased in these groups (all P<0.05). Conclusion:Both ACE2 and CAP can inhibit inflammation and protect the cardiovascular system, possibly by promoting the ACE2/Ang(1-9)/Ang(1-7) axis, thereby exerting a protective effect against VILI.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.