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.

Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ =869.89, P<0.05) and non-hemolytic febrile reactions (χ =812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.

Objective:To analyze the imaging characteristics of Stanford B aortic dissection in aortic CT angiography, in order to explore the possible related factors of aortic dissection combined with renal malperfusion and to analyze the morphological changes in each involved vessel after TEVAR.Methods:From January 2018 to December 2019, totally 148 patients of Stanford B aortic dissection underwent TEVAR in our hospital. The preoperative aortic CTA was analyzed, and all cases complicated with renal malperfusion were determined according to the clinical manifestation, laboratory examination and imaging results. The differences of morphological features between the patients with and without renal malperfusion and the possible correlative factors were analyzed.The different ischemic types of the involved renal arteries were analyzed, and the morphological changes of the involved vessels before and after the operation of TEVAR were compared.Results:The logistic regression analysis showed that the concave configuration of the tear at the renal artery level was the independent risk factor for renal malperfusion (right kidney OR=5.319, P=0.032; left kidney OR=12.879, P=0.007). The diameter of renal artery was the independent protective factor for renal malperfusion (right kidney OR=0.464, P=0.018; left kidney OR=0.685, P=0.016). Compared with preoperative CTA, the diameter of the involved renal artery was significantly enlarged after TEVAR, no matter which type of ischemia. Most of the dynamic ischemia (15/16) was improved after TEVAR; while static and mixed ischemia only partially improved after TEVAR (static 22/36, mixed 11/19) . Conclusion:The concave configuration of the renal artery level, and the diameter of renal artery are associated with renal malperfusion.The malperfusion can be improved in most cases of dynamic ischemia type vessels, while only can be partially improved in static and mixed types vessles.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

AIM To explore the effects of Zishui Qinggan Decoction on the mouse model of depression induced by chronic restraint stress(CRS)via ERK/GSK3β/CREB/BDNF signaling pathway.METHODS Except for those of the blank group,the mice of other groups were induced into depression models by CRS,and divided into the model group,the fluoxetine hydrochloride group(10 mg/kg)and the low,medium and high dose Zishui Qinggan Decoction groups(8.835,17.670 and 35.340 g/kg)for the corresponding drug intervention and simultanous CRS treatment.The mice had their sugar water preference experiment and behavior experiment on the 7th and 14th day after administration;the observation of the hippocampal morphological changes by HE staining,the detection of the superoxide dismutase(SOD)activity and malondialdehyde(MDA)level in serum by kits,the detection of levels of serum 5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)by ELISA,the detection of the hippocampal mRNA expressions of BDNF,TNF-α and IL-1β by RT-qPCR method,and the detection of the hippocampal protein expressions of ERK1/2,p-ERK1/2,GSK3β,p-GSK3β,CREB and BDNF by Western blot method 14 days after administration.RESULTS Compared with the model group,after 14 days of administration,both fluoxetine hydrochloride group and medium-dose Zishui Qinggan Decoction group displayed increased preference rate of sugar water(P<0.01),shortened immobility time of tail suspension and forced swimming(P<0.01),improved hippocampal damage of nerve cells,decreased levels of serum MDA,TNF-α and IL-1β(P<0.05,P<0.01),increased SOD activity and 5-HT level(P<0.05,P<0.01),decreased hippocampal mRNA expressions of TNF-α and IL-1β(P<0.01),and decreased expressions of BDNF mRNA and p-ERK1/2,p-GSK3β,CREB and BDNF proteins(P<0.05,P<0.01).CONCLUSION Zishui Qinggan Decoction can improve the depression-like behaviors in mice exposed to CRS,and its mechanism may be related to the regulation of hippocampal ERK/GSK3β/CREB/BDNF signaling pathway.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

OBJECTIVE To conduct a clinical comprehensive evaluation of potassium-competitive acid blockers （P-CAB） and provide reference for medical institutions to select new drugs， optimize drug catalogs， and use such drugs reasonably. METHODS clinical application guidelines， expert consensus， drug instructions， drug registration data （including phase Ⅲ clinical trials）， meta- analysis/systematic review of databases such as PubMed and CNKI related to Vonoprazan fumarate tablets， Tegorasen tablets， and Keverprazan hydrochloride tablets already on the market in China were collected and organized. Based on the Quick Guidelines for Drug Evaluation and Selection in Chinese Medical Institutions （Second Edition）， a comprehensive evaluation of the three P-CAB drugs was conducted from five dimensions: pharmaceutical characteristics， efficacy， safety， economy， and the other property. RESULTS The five dimensions of the three P-CAB were ranked from high to low as follows： Vonoprazan fumarate tablets （81.8 points）， Tegorasen tablets （75.7 points）， and Keverprazan hydrochloride tablets （75.6 points）. Among them， Vonoprazan fumarate tablets scored the highest in 4 dimensions of pharmaceutical properties， efficacy， economy， and the other property； but the safety score was slightly low. CONCLUSIONS The three types of P-CAB are comprehensively strongly recommended and demonstrated good clinical efficacy. Vonoprazan fumarate tablets have more advantages in terms of pharmaceutical properties， efficacy， and economy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment.Oral squamous cell carcinoma(OSCC),a representative hypoxic tumor,has a heterogeneous internal metabolic environment.To clarify the relationship between different metabolic regions and the tumor immune microenvironment(TME)in OSCC,Single cell(SC)and spatial transcriptomics(ST)sequencing of OSCC tissues were performed.The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data.The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-,normal-,or hypometabolic regions.CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others.Through CellPhoneDB and NicheNet cell-cell communication analysis,it was found that in the hypermetabolic region,fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts(iCAFs),and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12.The secretion of CXCL12 recruits regulatory T cells(Tregs),leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment.This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC,ST and TCGA bulk data,and highlights potential targets for therapy.