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:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment. Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγ antagonist GW9662 to confirm the involvement of this pathway in MaR1's effects. Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P＜0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P＜0.05).No significant difference in efficacy was observed between the 2 doses(all P＞0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1's protective effects.Real-time RT-PCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P＜0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P＞0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P＜0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P＜0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P＜0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P＜0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγ compared to the MaR1-LD group(all P＜0.05). Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Objective To investigate the risk factors for the formation of infectious stones among residents in western Fujian Province and construct a nomogram model for preoperative prediction of the risk of infectious stones. Methods Clinical data of 204 patients who received treatment for urinary tract stones at Longyan People′s Hospital Affiliated to Xiamen Medical University from October 2021 to November 2023 were analyzed. All patients underwent stone composition analysis. Univariate and multivariate Logistic regression analysis were used to screen independent risk factors for infectious stones, construct a nomogram model for predicting the risk of infectious stones, and the discriminative power and accuracy of the model was evaluated. Results Based on the results of stone composition analysis, 204 patients were divided into infectious stone group(56 cases) and non-infectious stone group(148 cases). Univariate and multivariate Logistic regression analysis showed that female (OR=2.602, 95%CI, 0.766 to 8.842, P=0.039), diabetes (OR=9.751, 95%CI, 2.547 to 17.332, P=0.001), long diameter of stones (OR=1.123, 95%CI, 1.046 to 4.207, P=0.031), moderate to severe hydronephrosis (OR=4.173, 95%CI, 1.256 to 13.865, P=0.020), high urine pH value (OR=6.078, 95%CI, 1.922 to 19.216, P=0.002), and positive urine culture (OR=6.060, 95%CI, 1.398 to 16.262, P=0.016) were independent risk factors for infectious stones. A nomogram model for predicting the risk of infectious stones was constructed based on independent risk factors. The area under the curve of this model for predicting infectious stones was 0.860, which was significantly larger than the area under the curve predicted by gender, diabetes, stone long diameter, degree of hydronephrosis, urine pH value, and urine culture results (P < 0.05). The model was validated by 1 000 internal resampling, with an average absolute error of 1.8%, indicating a high consistency between the predicted risk of infectious stones and the actual situation. Conclusion Female, diabetes, long diameter of stones, moderate to severe hydronephrosis, high urine pH value, and positive urine culture are independent risk factors for infectious stones among residents in western Fujian Province. The nomogram model constructed based on these factors can predict the risk of infectious stones preoperatively with high predictive efficiency.

Humans ; Leg/pathology* ; Skin Neoplasms/pathology* ; Lymphoma, Large B-Cell, Diffuse/pathology*

AIM: To investigate the effect of peripheral defocus spectacles and orthokeratology lenses on the control of axial length in children and adolescents with myopia.METHODS: Prospective study. A total of 71 cases(134 eyes)of children and adolescents with myopia who visited the Second Hospital of Longyan from June 2019 to June 2021 were selected. They were fitted with peripheral defocus spectacles for 12mo and then switched to orthokeratology lenses. The growth of axial length was observed at 3, 6, and 12mo after wearing peripheral defocus spectacles and orthokeratology lenses.RESULTS: The median axial length growth after wearing peripheral defocus spectacles and orthokeratology lenses for 12mo was 0.35 and 0.14mm, respectively. The axial growth at 3, 6, and 12mo after wearing orthokeratology lenses was lower than those after wearing peripheral defocus spectacles(P<0.001), and the growth rate of axial length was significantly reduced. The patients were divided into a rapid progression group(axial growth ≥0.4 mm, 29 cases, 54 eyes)and a non-rapid progression group(axial growth <0.4mm, 42 cases, 80 eyes)according to the axial growth of peripheral defocus spectacles for 12mo. The median axial growth after wearing peripheral defocus spectacles for 12mo in the two groups was 0.70 and 0.24mm, respectively, while the median axial growth after wearing orthokeratology lenses was 0.31 and 0.09mm, respectively. The growth rate was reduced by 56% and 63% respectively in the two groups after wearing orthokeratology lens. The axial growth of cases wearing orthokeratology lenses for 12mo in the non-rapid progression group was lower than that in the rapid progression group, and it did not change with age or diopter. There was no significant difference among different ages and different diopters in the rapid progression group(P>0.05). In the non-rapid progression group, axial growth of cases aged 7-12 years was higher than those aged 13-16 years(P<0.05), but there was no significant difference among different diopters(P>0.05).CONCLUSION: Orthokeratology lens is more effective than peripheral defocus spectacles in controlling axial growth in children and adolescents with myopia, and the control effect of orthokeratology lens on rapid-progressing myopia is remarkable.

Objective To investigate the effect of rehabilitation training combined with acupuncture ( RTA) on upper limb function of stroke patients by Kinect. Methods Stroke patients with upper limb dysfunction werrandomly divided into control group (rehabilitation training) and treatment group ( RTA), with 15 cases in each group. The modified Barthel Index ( MBI), Fugl Meyer assessment ( FMA), and Wolf motor function test (WMFT) were compared between two groups before and after treatment. The changes in motor time ( MT), motor unit number (MUN), index of curvature (IC), elbow flexion angle (EFA), shoulder flexion angle (SFA),and shoulder adduction angle ( SAA) during three actions, namely, placing forearm on the table, extending elbow and drinking water, were evaluated by Kinect and then compared between two groups before and after treatment. Results After 6 weeks of intervention, the scores of MBI, FMA, WMFT and elbow extension in treatment group were higher than those in control group (P<0. 05). The scores of MBI, FMA, WMFT and three actions after treatment were higher than those before treatment (P<0. 05). For three actions, the improvement of MT, MUN, IC, EFA, SFA, and SAA in treatment group were better than those in control group ( P< 0. 05). Compared with pre-treatment, for the action of forearm placement on the table and elbow extension, both treatment group and control group showed an increase in EFA (P<0. 05), and a decrease in MT, MUN, IC, SFA and SA (P<0. 05). For the action of drinking water, both treatment group and control group showed an increase in EFA and SAA (P< 0. 05), and a decrease in MT, MUN, IC and SAA ( P< 0. 05). Conclusions RTA can improve the upper limb function of stroke patients. Kinect can accurately reflect the changes in upper limb function of stroke patients, and it is suitable for clinical work.

OBJECTIVES: This study aims to determine the effects of low-level laser (LLL) on the expression of interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) in human periodontal ligament cells (HPDLCs) stimulated by high glucose; and identify the molecular mechanism of LLL therapy in the regulation of periodontal inflammation and bone remodeling during orthodontic treatment in diabetic patients. METHODS: HPDLCs were cultured in vitro to simulate orthodontic after loading and irradiated with LLL therapy. The cultured cells were randomly divided into four groups: low glucose Dulbecco's modification of Eagle's medium (DMEM)+stress stimulation (group A), high glucose DMEM+stress stimulation (group B), hypoglycemic DMEM+LLL therapy+stress stimulation (group C), and hyperglycemic DMEM+LLL therapy+stress stimulation (group D). Groups C and D were further divided into C1 and D1 (energy density: 3.75 J/cm²) and C2 and D2 (energy density: 5.625 J/cm²). Cells in groups A, B, C, and D were irradiated by LLL before irradiation. At 0, 12, 24, 48, and 72 h, the supernatants of the cell cultures were extracted at regular intervals, and the protein expression levels of IL-6, TNF-α, OPG, and RANKL were detected by enzyme-linked immunosorbent assay. RESULTS: 1) The levels of IL-6 and TNF-α secreted by HPDLCs increased gradually with time under static pressure stimulation. After 12 h, the levels of IL-6 and TNF-α secreted by HPDLCs in group A were significantly higher than those in groups B, C1, and C2 (P<0.05), which in group B were significantly higher than those in groups D1, and D2 (P<0.01). 2) The OPG protein concentration showed an upward trend before 24 h and a downward trend thereafter. The RANKL protein concentration increased, whereas the OPG/RANKL ratio decreased with time. Significant differen-ces in OPG, RANKL, and OPG/RANKL ratio were found among group A and groups B, C1, C2 as well as group B and groups D1, D2 (P<0.05). CONCLUSIONS 1) In the high glucose+stress stimulation environment, the concentrations of IL-6 and TNF-α secreted by HPDLCs increased with time, the expression of OPG decreased, the expression of RANKL increased, and the ratio of OPG/RANKL decreased. As such, high glucose environment can promote bone resorption. After LLL therapy, the levels of IL-6 and TNF-α decreased, indicating that LLL therapy could antagonize the increase in the levels of inflammatory factors induced by high glucose environment and upregulate the expression of OPG in human HPDLCs, downregulation of RANKL expression in HPDLCs resulted in the upregulation of the ratio of OPG/RANKL and reversed the imbalance of bone metabolism induced by high glucose levels. 2) The decrease in inflammatory factors and the regulation of bone metabolism in HPDLCs were enhanced with increasing laser energy density within 3.75-5.625 J/cm². Hence, the ability of LLL therapy to modulate bone remodeling increases with increasing dose.
Humans ; Osteoprotegerin ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/pharmacology* ; RANK Ligand/pharmacology* ; Periodontal Ligament/metabolism* ; Lasers ; Glucose/pharmacology*

The prevalence and mortality of cancer have been on the rise， and it has been the global leading cause of death. The causes of cancer are diverse， such as heredity， radiation， and carcinogens. The abnormality of cell cycle regulation is also one of the causes. Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides. Cell cycle is highly organized to ensure the integrity of genetic material. This process involves many regulatory genes and proteins. Cell cycle will be dysregulated when these proteins and genes change， resulting in the loss of control of cell proliferation， the inhibition of apoptosis， and finally the occurrence of tumor. At the moment， the therapies for cancer include traditional surgical resection， radiotherapy， chemical therapy， and targeted therapy. Chinese medicine has a wide range of sources and little side effect， which is worthy of further research and development. More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest， so as to improve the quality of life and prolong the survival time of patients with advanced tumors. This article first introduces the characteristics and related regulatory factors of each phase of cell cycle， and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle. Then， we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad， such as Cyclin-dependent kinase （CDK） inhibitors， cell division cycle 25 （CDC25） inhibitors， ataxia-telangiectasia-mutated-and-Rad3-related kinase （ATR） inhibitors， and checkpoint kinase 1 （CHK1） inhibitors. Finally， this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G₀/G₁ phase， S phase and G₂/M phase， in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.

Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Humans ; Solitary Fibrous Tumors/surgery*