The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

A qualitative analysis by high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF-MS/MS) was performed for the identification of main constituents in Gentiana veitchiorum. High-performance liquid chromatography (HPLC) was developed for the quantification of seven major components, including loganic acid (1), swertiamarin (2), gentiopicroside (3), sweroside (4), isoorientin (5), isoscoparin (6), and gentiournoside A (7). A total of 42 compounds, including 31 flavonoids, and 11 Iridoids, were identified based on their retention behaviors, and MS fragment information. Furthermore, regression equations for these seven chemical components were established, with good linear relationships (r2 > 0.9999), and the sample recovery rate was 97.02%-103.08%. This method was successfully applied for simultaneous determination of seven components in 7 batches of G. veitchiorum samples by HPLC-UV method. The method established in this study is simple and reliable, capable of qualitatively and quantitatively analyzing the main chemical components of G. veitchiorum, and is applicable to its quality evaluation.

Tubal ciliary movement is one of the essential transport mechanisms for female fertility, playing a key role in facilitating oocyte pickup and transporting the fertilized ovum. This movement is mediated by multiciliated cells and regulated by specific proteins and hormones that modulate ciliary number, length, polarity, beat frequency, and amplitude to ensure proper function. Genetic mutations, inflammatory stimuli, and hormonal fluctuations can impair ciliary activity or induce ciliary apoptosis, leading to ciliary dysfunction. Disorders of tubal ciliary movement are frequently observed in primary ciliary dyskinesia, pelvic inflammatory disease, polycystic ovary syndrome, and endometriosis, conditions commonly associated with female infertility. These disorders manifest as structural abnormalities of cilia, disrupted polarity, shortened ciliary length, reduced ciliary count, and decreased beat frequency and amplitude. Understanding the role of tubal ciliary movement in female infertility-related diseases, through immunohistochemistry and ultrastructural analysis, helps clarify underlying infertility mechanisms. Identifying abnormal inflammatory factors, hormonal environments, and gene expression, combined with advanced techniques for measuring ciliary protein and beat frequency, may offer novel clinical targets for early prevention and treatment of female infertility.
Humans ; Female ; Infertility, Female/etiology* ; Cilia/physiology* ; Polycystic Ovary Syndrome/physiopathology* ; Fallopian Tubes/physiopathology* ; Endometriosis/complications* ; Pelvic Inflammatory Disease/complications*

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective:To investigate the effects of psychological stress on odour preference choices of mice and the related neural mechanisms.Methods:C57BL/6 male mice were randomly divided into control group and stress group.An unpredictable mild stress(UMS)model was established in the stress group using mild stress stimuli like fasting,restraint,and circadian rhythm disruption combined with open field tests.Then,the preferences for food extract odour and female urine odour was examined in control and UMS male mice.The specific brain regions activated during dual odour preference tests in UMS mice were identified by the expression of the neuronal activity-related c-Fos.Further,chemogenetic manipulation was used to validate key brain areas influencing UMS mice's odour preferences.Results:Control mice showed no clear preference for either odour,while UMS mice demonstrated a significant preference for fe-male urine.During the dual odour preference test,an increase in c-Fos positive neurons is observed in the medial pre-optic area(MPOA)and posterior dorsal part of medial amygdala(MePD)of UMS mice.Activating MePD resulted in male mice preferring female urine odour,while inhibiting MePD reduced this preference.The manipulation of MPOA did not affect the outcome of the dual-choice odour preference test.Conclusion:UMS male mice has a significant prefer-ence for female urine odour,and MePD is a key brain region regulating this behavior.

AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.

Objective:To analyze the prognostic factors of children with septic shock in the pediatric intensive care unit.Methods:The clinical data of children diagnosed with septic shock in the pediatric intensive care unit of Guiyang Maternal and Child Health Hospital from April 2018 to April 2022 were retrospectively collected,and the children were divided into the death group and the survival group according to seven days regression.The basic data of the two groups were statistically compared，and the relationship between lactic acid，vasoactive-inotropic score one hour after admission，time of antibiotic initiation，serum potassium，serum sodium，serum calcium，serum troponin T，fluid resuscitation volume in the first hour，glutamyl aminotransferase，creatinine，total leukocyte count，C-reaction protein，brain natriuretic peptide were compared.The risk factors affecting the death of children were analyzed by Logistic regression.The relationship between fluid resuscitation volume in the first hour and prognosis was analyzed using the receiver operator characteristic (ROC) curve.Results:（1）A total of 67 children were included，19 died and 48 survived.（2）The first-hour liquid resuscitation dose in the survival group was lower than that in the death group，and the difference was statistically significant（ P<0.05）.（3）The ROC curve showed that the optimal cut-off of the first-hour liquid resuscitation dose was 25 mL/kg，with a sensitivity of 57.9% and a specificity of 72.9%.（4）In unifactorial analysis，lactic acid in the first hour of admission，early lactic acid after resuscitation，serum calcium，serum troponin T，alanine aminotransferase，combined septic encephalopathy，Glasgow coma score，and pediatric critical illness score were all risk factors for death in children within seven days（ P<0.05）.(5) Multivariate Logistic regression analysis showed that serum calcium（ OR=1.435， P=0.001）and lactic acid value after resuscitation（ OR=0.040， P=0.021）were independent risk factors for death in septic shock. Conclusion:The higher the total fluid resuscitation in the first hour，the higher the fatality rate.Serum calcium and early lactic acid after resuscitation are independent risk factors for death in children within seven days.