Immune checkpoint blockade therapy has demonstrated remarkable efficacy in treating various malignancies; however, its clinical application remains challenged by low response rates and immune-related adverse events. Immunoglobulin superfamily member 11 (IGSF11), an inhibitory immune checkpoint molecule, serves as a specific ligand for the V-domain immunoglobulin suppressor of T cell activation (VISTA). Through the IGSF11/VISTA axis, it suppresses T cell function and represents a promising novel target for cancer immunotherapy. IGSF11 is widely expressed across multiple tumor types, though its regulatory mechanisms vary depending on the malignancy. Studies have confirmed that blocking the IGSF11-VISTA interaction or specifically inhibiting IGSF11 exerts antitumor effects. While IGSF11 is closely associated with patient prognosis, its prognostic significance differs among cancer types. This review systematically summarizes the structural characteristics of IGSF11, its regulatory mechanisms, interaction with VISTA, and functional role within the tumor microenvironment.
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Humans ; Immunotherapy ; Neoplasms/metabolism* ; B7 Antigens/chemistry* ; Animals ; Molecular Targeted Therapy ; Tumor Microenvironment

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

Objective To analyze the clinical characteristics and interventional treatment effects of pa-tients with renal arteriovenous fistula in this hospital over the past 10 years.Methods A retrospective analy-sis was conducted on the clinical and imaging data of 40 patients with renal arteriovenous fistula who were treated in this hospital from October 2012 to October 2022.After classifying the fistula type using digital sub-traction angiography(DSA),an individualized embolization plan was developed by a vascular surgery team.Postoperatively,the embolization materials,embolization success rate,clinical success rate,perioperative renal function changes and complications were analyzed.Results A total of 29 cases(72.5%)had acquired renal arteriovenous fistula,while 11 cases(27.5%)had non-acquired renal arteriovenous fistula.Forty-three super-selective transcatheter arterial embolization(TAE)procedures were performed,achieving a technical success rate of 100.0%(40/40)and a clinical success rate of 95.0%(38/40).The mean serum creatinine levels after TAE were(91.39±23.72)mmol/L in the non-acquired group and(105.94±35.51)mmol/L in the acquired group.No statistically significant difference was observed in perioperative serum creatinine changes between the two groups(P=0.095).No severe complications such as renal function deterioration occurred postopera-tively in any patient.Conclusion Gross hematuria serves as the primary clinical manifestation of renal arterio-venous fistula,with abdominal pain being more prevalent in non-acquired renal arteriovenous fistula.The em-bolization approach combining coils with polyvinyl alcohol particles demonstrates favorable safety and efficacy in treating renal arteriovenous fistula.

Humans ; Gastrointestinal Microbiome ; Constipation/therapy* ; Probiotics/therapeutic use* ; Patients

Objective To analyze the application value of uterine artery flow and cerebral placental rate(CPR)in diagnosing fetal growth restriction(FGR).Methods A total of 114 pregnant women with clinically diagnosed late-onset FGR who were hospitalized in Jiangxi Maternal and Child Health Hospital from January 2021 to June 2022 were assigned to study group,and 122 pregnant women with normal intrauterine development were assigned to control group.The blood flow parameters of uterine artery(UtA),umbilical artery(UA)and middle cerebral artery(MCA)in two groups were determined by ultrasound,and CPR in two groups was calculated.The blood flow difference and pregnancy outcome of two groups were compared.Receiver operating characteristic(ROC)curve was used to analyze the application value of UtA and CPR alone and combined in the clinical diagnosis of FGR.Results The UtA resistance index(RI)of pregnant women in study group was higher than that of control group,the fetal UA blood flow parameter was higher than that of control group,the MCA blood flow parameter and the CPR value were both lower than those of control group,the differences were statistically significant(P<0.05).The birth weight and 1min Apgar score of study group were lower than those of control group(P<0.001).In addition,the incidence of emergency cesarean section operation,premature delivery and neonates transferred to neonatal intensive care unit(NICU)due to various complications in study group were significantly higher than those in control group(P<0.05).ROC curve showed that in predicting FGR,the area under the curve(AUC)of UtA-RI was 0.82(95%CI:0.77-0.88).The predictive efficiency of CPR was 0.75(95%CI:0.69-0.81).The combination of UtA-RI and CPR parameters had the highest efficiency in predicting FGR,with an AUC of 0.92(95%CI:0.89-0.95).Conclusion CPR combined with UtA-RI monitoring has clinical application value for early detection of FGR,guiding intervention,and improving adverse perinatal outcomes.

mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by in vitro cytotoxicity and in vivo biosafety. First, we characterized the chemical composition of the cationic lipid peptides by nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) and time-of-flight mass spectrometry (MS). The results of particle size and potential tested by dynamic light scattering particle size analysis showed that at a nitrogen/phosphorus (N/P) ratio of 20, the RLS/mRNA composite assemblies formed homogeneous nanoparticles with an average particle size of about 220 nm and a surface ζ potential of about +21 mV. In vitro gene transfection, the transfection experiments demonstrated that RLS exhibited 1.2-fold higher transfection efficiency in human embryonic kidney 293 cells (HEK293) and 3-fold higher transfection efficiency in rat mesenchymal stem cells (MSC) compared to Lipofectamine 2000. In addition, after microinjection of RLS into zebrafish embryos, we evaluated the survival, hatching, and teratogenicity rates, all of which confirmed its favorable in vivo safety profile. Thus, this amphiphilic cationic lipid peptide RLS, enriched with branched arginine, exhibits excellent mRNA delivery properties and safety. These findings highlight its potential as a promising gene therapy tool.

Objective To observe the clinical efficacy of modified Shehuang Ointment(mainly composed of Cnidii Fructus,Phellodendri Chinensis Cortex,and Zanthoxyli Pericarpium)for the treatment of facial seborrheic dermatitis(SD).Methods Seventy-two patients with facial SD were randomly divided into observation group and control group,with 36 patients in each group.Both groups of patients were given oral use of Acrivastine Capsules and Vitamin B6 Tablets,and additionally,the observation group was given topical application of modified Shehuang Ointment and the control group was given topical application of 2%Ketoconazole cream.The course of treatment covered 4 weeks.The changes of clinical symptom scores and dermatology life quality index(DLQI)scores in the two groups were observed before and after treatment,and the clinical efficacy and safety of the two groups were also evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 88.89%(32/36),and that of the control group was 72.22%(26/36).The intergroup comparison showed that the efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the clinical symptom scores of erythema,scales,grease,rash area,itchiness and other clinical symptoms of the patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the clinical symptom scores of the observation group were significantly lower than those of the control group,the differences being statistically significant(P＜0.05).(3)After treatment,the DLQI scores of patients in the two groups were significantly lower than those before treatment(P＜0.05),and the DLQI scores in the observation group were significantly lower than those in the control group after treatment,the difference being statistically significant(P＜0.05).(4)During the treatment period,no significant adverse reactions occurred in the two groups of patients,with high safety.Conclusion The conventional western medicine treatment combined with topical application of modified Shehuang Ointment exerts certain effect in the treatment of facial SD,which can effectively relieve the clinical symptoms and improve the quality of life of patients.

Objective:To analyze the role of home medical and nursing care team in the service system of home disabled elderly.Methods:A total of 100 home disabled elderly managed by our hospital from Jan to Dec 2022 were enrolled,and the home medical and nursing care teams strengthened home rehabilitation nursing services and guidance,health risk guidance,psychological support,and nutrition guidance and intervention.The management results before and after intervention was compared.Results:After intervention,the mastery of health risk management,psychological support and nutritional intervention,and the compliance rate of rehabilitation exercise were higher than those before intervention(P＜0.05).The incidence of pressure injury was lower than that before intervention(P＜0.05).After intervention,the satisfaction rate of the elderly to the work of the home medical and nursing care team was 95%.Conclusion:Home medical and nursing care team plays an important role in the nursing service system of the disabled elderly,and play an important role in the construction of a three-level service health management system of institution-community-home.