By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

ObjectiveTo explore the diagnostic value of resting-state functional magnetic resonance imaging (rs-fMRI) for mild cognitive impairment (MCI) stage of Alzheimer's disease (AD), and to investigate the changes in brain functional connectivity in default mode network (DMN) and medial temporal lobe (MTL) regions. MethodsLiteratures were retrieved from multiple databases including CNKI, PubMed, Medline, and Embase, etc. from January, 2020 to October, 2025, investigating the changes in functional connectivity of DMN and MTL in patients with MCI compared to health control (HC) using rs-fMRI. Two researchers independently screened and extracted the literatures and methodological quality was assessed using QUADAS-2. Review Manager 5.4 was used to perform a meta-analysis of neuroimaging indicators in MCI patients and HC subjects. Stata and SDM were utilized to summarize diagnostic efficacy and brain functional connectivity, calculating the over all sensitivity, specificity and summary receiver operating characteristic-area under the curve (SROC-AUC). Deeks funnel plots were drawn, literature weights were analyzed, and subgroup analyses were conducted. ResultsA total of ten literatures were ultimately included, involving 1 010 patients with MCI and 1 714 HC subjects. MCI patients showed decreased or abnormal blood oxygen level dependence signals in DMN, focusing on bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex. The SROC-AUC was 0.91. In MTL, there was a characteristic decrease of spontaneous neural functional connectivities between the hippocampus and other regions, reflecting the obstruction of information transmission from episodic memory to the central nodes. Abnormal functional connectivity in DMN and MTL resulted in compensatory resting-state functional connectivity enhancement in other subnetworks or local functional connections, such as frontoparietal network and the hippocampal-parietal network. Abnormal activation of mPFC suggested atrophy of the hippocampus or abnormal brain function. The decline in functional connectivity between DMN and MTL indicated impairment of memory and information processing in the early stage. ConclusionThe early functional decoupling between DMN and MTL is a crucial neural mechanism at the MCI stage of AD, providing important neuroimaging evidence for the early diagnosis of AD.

Background Silicosis, an occupational lung disease induced by chronic silica (SiO₂) exposure, is pathologically defined by progressive pulmonary fibrosis, and its associated molecular mechanisms are not yet fully elucidated. Objective To understand the critical role of macrophage-derived vesicles in silicotic pulmonary fibrosis via their carried complement component 1r (C1R). Methods Through integrated analysis of human plasma vesicle proteomics and spatial transcriptomics in silicosis mouse models, the key molecular C1R was identified in silicotic fibrosis. Spatial transcriptomic data were further employed to analyze the expression distribution of C1R in lung tissues. In animal experiments, a mouse silicosis model was established via tracheal instillation of silica dust, followed by pulmonary fibrosis assessed by Sirius Red staining, and C1R expression levels in plasma and lung tissue vesicles examined by Western blot. In cellular experiments, an in vitro model was constructed by stimulating macrophages with silica. Extracellular vesicles isolated from this system were then co-cultured with mouse lung fibroblasts (MLG),followed by intervention with a C1R-neutralizing antibody. Results The proteomic analysis of human plasma vesicles revealed a significant upregulation of C1R in silicosis patients, confirmed by Western blot. The spatial transcriptomics in silicotic mice indicated elevated C1R expression in lung tissues after 56 d of SiO₂ exposure, colocalizing with fibrotic lesions. The results of Western blot further demonstrated increased C1R levels in both lung tissue-derived and peripheral blood-derived vesicles during silicosis progression, consistent with the findings in an ex vivo macrophage model. The results of functional assays demonstrated that macrophage-derived vesicles significantly increased the expression of fibrosis markers, including fibronectin 1 (FN1), collagen type I alpha 1 (COL1A1), and alpha-smooth muscle actin (α-SMA), as well as the migratory capacity of lung fibroblasts; these effects were blocked by the C1R-neutralizing antibody. Conclusion Macrophage vesicles drive fibroblast activation and migration through C1R. Since a C1R-neutralizing antibody blocks this pro-fibrotic effect, C1R represents a key mediator in silicosis and thus is considered a new potential therapeutic target.

Objective: To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome. Methods: One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website. Results: There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways. Conclusion Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.

Objective:To analyze the epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia and explore the related factors of these two health problems.Methods:In September 2022, a stratified random cluster sampling method was employed to select 188 635 children and adolescents aged 6-18 in Inner Mongolia for physical examinations and questionnaire surveys. Data on height, weight, as well as dietary behavior, physical activity, classroom environment, academic tasks, writing posture, and screen behavior were collected. The epidemiological characteristics of wasting, spinal curvature abnormalities and multimorbidity were analyzed. Additionally, a multivariate logistic regression model was used to analyze the factors associated with wasting, spinal curvature abnormalities and multimorbidity.Results:A total of 188 635 children and adolescents aged 6-18 years participated in this study, including 95 393 boys (50.6%) with an average age of (11.53±3.32) years. The detection rate of wasting was 3.79%, with a higher detection rate in boys (4.18%) than in girls (3.38%) ( P<0.001). The detection rate of spinal curvature abnormalities was 3.64%, with a higher detection rate in girls (4.04%) than in boys (3.25%) ( P<0.001). The detection rate of multimorbidity between wasting and spinal curvature abnormalities was 0.17%, and there was no statistically significant difference between genders ( P>0.05). The detection rates of wasting, spinal curvature abnormalities, and multimorbidity all increased with age ( P t<0.001). The multivariate logistic regression analysis showed that, after adjusting for gender, age, urban/rural status, and school grade, compared to children and adolescents who exercised ≥1 hour of moderate-to-vigorous physical activity (MVPA) for at least 5 days per week and had daily screen time <2 hours, those who exercised <5 days per week ( OR=1.28, 95% CI: 1.19-1.37) and had daily screen time ≥2 hours ( OR=1.11, 95% CI: 1.03-1.19) had a higher risk of wasting. Compared to children and adolescents who had ≥5 physical education (PE) classes per week, adjusted desk and chair height,<1 hour of after-school study/writing time, and whose parents or teachers rarely or never reminded them about posture, those with <5 PE classes per week ( OR=1.11, 95% CI: 1.02-1.21), unadjusted desk and chair height ( OR=1.08, 95% CI: 1.01-1.15),≥1 hour of after-school study/writing time ( OR=1.15, 95% CI: 1.07-1.24), frequent reminders from parents ( OR=1.16, 95% CI: 1.09-1.23), and frequent reminders from teachers ( OR=1.10, 95% CI: 1.04-1.16) had a higher risk of spinal curvature abnormalities. Compared to children and adolescents who did not consume sugary drinks daily, exercised ≥1 hour of MVPA for at least 5 days per week, and whose teachers rarely or never reminded them about posture, those who consumed sugary drinks daily ( OR=1.61, 95% CI: 1.00-2.46), exercised <5 days per week ( OR=1.33, 95% CI: 1.01-1.79), and had teachers who frequently reminded them about posture ( OR=1.35, 95% CI: 1.05-1.75) had a higher risk of multimorbidity between wasting and spinal curvature abnormalities. Conclusion:The detection rates of wasting, spinal curvature abnormalities and multimorbidity among children and adolescents aged 6-18 in Inner Mongolia are generally low, with an increasing trend observed with age. Both lifestyle and school environmental factors are associated with wasting, spinal curvature abnormalities and multimorbidity.

Objective To investigate the proportions of myeloid-derived suppressor cells(MDSCs)and their subsets,including poly-morphonuclear MDSCs(PMN-MDSCs),early-stage MDSCs(e-MDSCs),monocytic MDSCs(M-MDSCs),and lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)positive PMN-MDSCs,in the peripheral blood of ovarian cancer(OC)patients and ana-lyze their correlations with clinicopathological parameters of the patients.Methods The proportions of MDSCs and their subsets in the peripheral blood of 38 OC patients(OC group)and 46 healthy individuals(healthy control group)were detected by flow cytometry.The levels of serum IL-10 and TGF-β were detected using ELISA.The OC group was further divided into LOX-1 high and low expres-sion subgroups based on the median proportion of LOX-1+PMN-MDSCs in MDSCs.Results The proportions of MDSCs,PMN-MDSCs,and LOX-1+PMN-MDSCs in the peripheral blood mononuclear cells(PBMCs)of the OC group were significantly higher than those in the healthy control group(U=492,P＜0.001;t=8.741,P＜0.000 1;U=223,P＜0.000 1).The proportions of M-MDSCs and e-MDSCs in the OC group were significantly lower than those in the healthy control group(t=4.366,P＜0.000 1;t=6.927,P＜0.000 1).The proportion of LOX-1+PMN-MDSCs in the lymph node metastasis group of OC patients was significantly higher than that in the non-metastasis group(t=2.249,P＜0.05).The levels of serum IL-10 and TGF-β in the OC group were significantly higher than those in the healthy control group(P＜0.05).In addition,the level of serum TGF-β in the LOX-1 high expression group was significantly higher than that in the LOX-1 low expression group(t=2.302,P＜0.05).Conclusion The proportion of LOX-1+PMN-MDSCs in the peripheral blood of OC patients is significantly increased and closely related to lymph node metastasis.

Pancreaticoduodenectomy is a difficult and risky operation, and postoperative bleeding is one of its serious complications. Fully understanding the potential risk factors of postoperative pancreatic bleeding and taking effective preventive measures, conducting scientific assessment and reasonable treatment decisions for postoperative bleeding are the keys to reducing the mortality rate after PD and increasing the safety of the surgery. This article briefly expounds the etiology, diagnosis, treatment and preventive measures of postoperative bleeding after pancreaticoduodenectomy.