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.

Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Objective Based on the radiomics features extracted from the unenhanced CT images of the lower abdomen, a variety of machine learning models were constructed to explore their application value in the assessment of split renal function. Methods A retrospective analysis was conducted on the unenhanced CT images from 240 single kidneys in patients with clinically suspected renal dysfunction. Based on the results of single-photon emission computed tomography renal dynamic imaging, the cases were classified into the normal glomerular filtration rate group (n=118) and the decreased glomerular filtration rate group (n=122). The region of interest was outlined on the unenhanced CT images and the radiomics features were extracted. The features were selected by correlation analysis and least absolute shrinkage and selection operator, and the machine learning models were constructed based on the algorithms of decision tree, support vector machine, random forest, logistic regression, and extreme gradient boosting. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were calculated to compare the performance of different models. Results Sixteen radiomics features were selected for constructing the machine learning models. The support vector machine model showed relatively high performance for the assessment of split renal function on the test set, with an area under the receiver operating characteristic curve value of 0.883 (95% confidence interval: 0.804-0.961), an accuracy of 0.778, a sensitivity of 0.811, and a specificity of 0.743. Conclusion The machine learning models constructed based on unenhanced CT radiomics can be used to preliminarily assess split renal function, which provides an innovative, convenient, and safe method for clinical diagnosis and has positive significance for treatment.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease with a polygenic genetic background. Its etiology remains unclear， and its pathogenesis is complex and refractory， collectively posing significant challenges in its treatment and greatly affecting the physical and mental health of patients. With the advantages of multi-target and multi-pathway treatment， traditional Chinese medicine has shown unique efficacy and value in the diagnosis and treatment of psoriasis. Modern doctors have a lot of discussion on psoriasis， and most of them tend to treat the disease by solving disorders of the blood system. They think that the disease is closely related to the "heat in the blood". Combining the clinical characteristics and accompanying symptoms of psoriasis， this article traced the causes of "heat in the blood" in psoriasis and believed that multiple internal and external factors have prevented the smooth circulation of Qi. Yang Qi Fuyu （stagnation） and transformation into heat and toxicity is the source of "heat in the blood" in psoriasis. Furthermore， it was proposed that "Fuyu" is the core pathogenesis of psoriasis. The etiology of "Fuyu" is complex， such as external wind and cold pathogens， emotional injuries， internal accumulation of dampness， and deficiency of healthy Qi， all of which can disrupt the ascending and descending movement of Qi， impede the circulation of Qi and fluids， close the pores and skin texture， and subsequently lead to stagnation. Based on the above understanding， "resolving stagnation" is crucial for treating the disease. Many doctors have explored the treatment ideas of psoriasis from the perspectives of dispelling wind， warming cold， regulating Qi， eliminating dampness， tonifying deficiency， and external treatment， aiming to remove the causes， promote the circulation of Qi and fluids， and resolve stagnation and heat. Clinical studies have shown that the therapies can relieve clinical symptoms， reduce recurrence rate， and improve quality of life， which also have good safety in the treatment of psoriasis. This article discussed the treatment of psoriasis from the perspective of "Fuyu"， enriching the understanding of TCM regarding the etiology and pathogenesis of psoriasis. It is aiming to serve as an effective supplement to the "treating by solving disorders of the blood system" approach and provide a reference for clinical diagnosis and treatment of psoriasis.