Mainly based on the "constitution-syndrome-disease location correlation" approach， this study constructs a traditional Chinese medicine （TCM） framework for understanding hypertension comorbidities. From the perspective of shared constitutional predispositions and similar pathomechanistic characteristics， hypertension comorbidity should not be regarded as a simple aggregation of multiple diseases. Rather， it is generally rooted in biased constitutions such as yin-deficiency， qi-deficiency， yang-deficiency， phlegm-dampness， dampness-heat， and blood-stasis constitutions， accompanied by the long-term interplay of pathogenic mechanisms involving wind， fire， phlegm， stasis， and deficiency， and gradually manifests as comorbidities affecting different systems through the evolution of disease locations related to the liver， heart， spleen， and kidney. On this basis， cardiac-， cerebral-， renal-， and metabolic-related comorbidities are taken as the major categories， and their characteristics related to constitution， syndrome， and disease location are systematically summarized to clarify the correspondence between shared pathomechanisms and predominant disease locations， and to propose corresponding prevention and treatment strategies. This framework further incorporates constitution-based stratification into risk stratification for prospective intervention， and takes syndrome as the central link in developing multi-disease treatment strategies such as boosting qi and activating blood， as well as resolving phlegm and unblocking collaterals. A clinical pathway is thereby proposed， encompassing constitution assessment， syndrome differentiation， comorbidity risk stratification， integrated traditional Chinese and western medicine intervention， and follow-up feedback. This study aims to provide a reference for the theoretical development and collaborative management of hypertension comorbidities in TCM.

AIM:To investigate the potential mechanism of neutrophil extracellular traps(NETs)in the pla-centa during the pathogenesis of preeclampsia(PE).METHODS:Differential neutrophil infiltration in PE versus normo-tensive placentas was assessed using placental transcriptome sequencing data.Single-cell sequencing analysis of GSE173193 dataset was conducted to evaluate the expression of NETs formation-related genes in neutrophils from PE pla-centa and control placenta.Immunofluorescence and ELISA were used to measure NETs levels in placental tissues.Fol-lowing NETs generation and treatment of human extravillous trophoblast(EVT)HTR8/Svneo strain with NETs,RNA se-quencing was utilized to identify potential signaling pathways through which NETs regulate trophoblast function.RE-SULTS:Neutrophil infiltration,and expression of NETs formation critical genes,MPO(myeloperoxidase)and ELANE(elastase,neutrophil expressed),in neutrophils were significantly increased in PE placentas compared with controls.The level of NETs was elevated in PE placentas as well.The NETs significantly inhibited the migration of HTR8/Svneo cells.Disrupted F-actin arrangement,aggregate formation,and reduced paxillin expression were observed in NETs-treated HTR8/Svneo cells.Single-cell sequencing analysis revealed that focal adhesion and stress fiber pathways were down-regu-lated in the EVT of PE placenta.CONCLUSION:Neutrophil infiltration and NETs formation were increased in PE.The NETs may inhibit EVT migration by inducing stress fiber disassembly and down-regulating paxillin expression,thereby dis-rupting cytoskeletal organization and focal adhesion formation.

AIM:To investigate the potential mechanism of neutrophil extracellular traps(NETs)in the pla-centa during the pathogenesis of preeclampsia(PE).METHODS:Differential neutrophil infiltration in PE versus normo-tensive placentas was assessed using placental transcriptome sequencing data.Single-cell sequencing analysis of GSE173193 dataset was conducted to evaluate the expression of NETs formation-related genes in neutrophils from PE pla-centa and control placenta.Immunofluorescence and ELISA were used to measure NETs levels in placental tissues.Fol-lowing NETs generation and treatment of human extravillous trophoblast(EVT)HTR8/Svneo strain with NETs,RNA se-quencing was utilized to identify potential signaling pathways through which NETs regulate trophoblast function.RE-SULTS:Neutrophil infiltration,and expression of NETs formation critical genes,MPO(myeloperoxidase)and ELANE(elastase,neutrophil expressed),in neutrophils were significantly increased in PE placentas compared with controls.The level of NETs was elevated in PE placentas as well.The NETs significantly inhibited the migration of HTR8/Svneo cells.Disrupted F-actin arrangement,aggregate formation,and reduced paxillin expression were observed in NETs-treated HTR8/Svneo cells.Single-cell sequencing analysis revealed that focal adhesion and stress fiber pathways were down-regu-lated in the EVT of PE placenta.CONCLUSION:Neutrophil infiltration and NETs formation were increased in PE.The NETs may inhibit EVT migration by inducing stress fiber disassembly and down-regulating paxillin expression,thereby dis-rupting cytoskeletal organization and focal adhesion formation.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Aim Toinvestigatethepro-angiogenic effects of Danshensu derivative ADTM and explore its underlying possible signaling pathway using zebrafish embryosasinvivomodels.Methods Theangiogenesis activities of ADTM were determined in experimental models of normal and VEGFR tyrosine kinase inhibitorⅡ(VRI )-induced vascular defective zebrafish embry-os.Embryos were treated with various concentrations (50,100,200 μmol · L-1 ) of ADTM for indicated time.The diameter and the numbers of endothelial cells of zebrafish SIVs were evaluated,respectively.In VRI model,the number of intact and defective ISVs in each zebrafish embryo was counted.The total RNA of zebrafish embryos was extracted and transcriptional profiling was analyzed by deep sequencing.Quantita-tive real-time PCR(qPCR)was performed to 4 genes selected from transcriptional profiling to validate the data collected from transcriptome analysis.Results ADTMsignificantlyincreasedsubintestinalvessels (SIVs)diameter in a concentration-dependent manner in normal zebrafish as well as restored VRI-induced blood vessels defect in VRI-exposed zebrafish. The transcriptome data analysis demonstrated that 19 signif-icantly changed genes were mapped to insulin signaling pathway.The qPCR data are in good agreement with those obtained by deep sequencing and support the consistency between the two methods for determining relative expression levels in the zebrafish model.Con-clusion Inzebrafishmodel,ADTMexhibitsthe effects of angiogenesis and blood vessel restoration. The underlying mechanism may be involved in the acti-vation of insulin signaling pathway.

Objective To investigate the influence of lidocaine on systemic inflammatory response to cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG) .Methods Twenty ASA Ⅱ or Ⅲ patients of both sexes (13 males, 7 females) aged 47-67 yrs weighing 62-82 kg undergoing CABG were randomly divided into 2 groups of 10 each: control group (C) and lidocaine group (L). In group L lidocaine infusion was started as soon as the pericardium was cut open and maintained at 4 mg?min-1 until the end of the surgery. Another dose of lidocaine (4 mg?kg-1) was added to the prime. In control group normal saline (NS) was given instead of lidocaine in the same volume and at the same speed. Blood samples were taken from radial artery before CPB (T0, baseline) and at 1, 10 and 60 min after release of the aortic cross-clamp (T1,2,3) for determination of plasma concentration of TNF-?, IL-6, IL-10 and PMN count. Plasma lidocaine concentration was determined at 10 and 60 min after initiation of CPB and at the end of surgery in 5 patients in group L. Results The two groups were comparable with respect to age, sex ratio (M/F), body weight, CPB time and aortic cross-clamping time. The mean plasma lidocaine concentration was (4.1?0.5)?g?ml-1, (4.6?0.7) ?g?ml-1 and (5.9?0.9)?g?ml-1 at 10, 60 min of CPB and end of surgery respectively in group L. Plasma concentrations of TNF-?, IL-6, IL-10 and PMN count were significantly increased at T1,2,3 as compared to the baseline values at T0 in both groups. The plasma concentrations of TNF-? and IL-6 were significantly lower while those of IL-10 were significantly higher at T1-3 in group L than in group C. Conclusion Lidocaine can inhibit the inflammatory response induced by CPB in patients undergoing CABG.