Clinical Impact of Operating Room Nursing Pathways on Hospitalization Duration and Consciousness Status in Patients Undergoing Emergency Craniocerebral Injury Surgery.

Background: Craniocerebral injuries carry high disability and mortality rates. In clinical practice, timely determination of the condition and immediate rescue interventions are crucial for patients with emergency craniocerebral injuries. Nurses play a pivotal role in providing proactive nursing services to save patients' lives. Objective: This study aims to examine the practical implications of implementing operating room nursing pathways in the care of patients undergoing emergency craniocerebral injury surgery. Design: A randomized controlled study was conducted. Setting: The study was conducted at the Department of Operating Room at Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine. Participants: A total of 80 patients undergoing emergency craniocerebral injury surgery in our hospital from August 2020 to August 2022 were included. They were randomly divided into control and observation groups through a lottery, with 40 cases in each. Interventions: The control group received conventional nursing, while the observation group received operating room nursing pathways. Primary Outcome Measures: (1) Surgical preparation time, surgical time, and hospitalization time; (2) Pupil scores; (3) Brain injury grading; and (4) Nursing satisfaction score. Results: The observation group exhibited a significant decrease in surgical preparation time and hospitalization time compared to the control group (P < .05). After the intervention, severe craniocerebral injury pupil scores in the observation group showed improvement compared to the control group (P < .05). The total satisfaction rate in the observation group (92.5%) was higher than that in the control group (80.0%) (P = .012). Conclusions: The application of operating room nursing pathways in patients undergoing emergency craniocerebral injury surgery can lead to a shortened length of stay, substantial improvement in patients' consciousness status, and high satisfaction rates from both patients and their family members. This intervention holds significant clinical value and merits further promotion.

Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite.

Tumors employ various strategies to evade immune surveillance. Central nervous system (CNS) has multiple features to restrain immune response. Whether tumors and CNS share similar programs of immunosuppression is elusive. Here, we analyze multi-omics data of tumors from HER2+ breast cancer patients receiving trastuzumab and anti-PD-L1 antibody and find that CNS-enriched N-acetyltransferase 8-like (NAT8L) and its metabolite N-acetylaspartate (NAA) are overexpressed in resistant tumors. In CNS, NAA is released during brain inflammation. NAT8L attenuates brain inflammation and impairs anti-tumor immunity by inhibiting cytotoxicity of natural killer (NK) cells and CD8+ T cells via NAA. NAA disrupts the formation of immunological synapse by promoting PCAF-induced acetylation of lamin A-K542, which inhibits the integration between lamin A and SUN2 and impairs polarization of lytic granules. We uncover that tumor cells mimic the anti-inflammatory mechanism of CNS to evade anti-tumor immunity and NAT8L is a potential target to enhance efficacy of anti-cancer agents.

Causal associations between modifiable risk factors and isolated REM sleep behavior disorder: a mendelian randomization study.

Objectives: This Mendelian randomization (MR) study identified modifiable risk factors for isolated rapid eye movement sleep behavior disorder (iRBD). Methods: Genome-wide association study (GWAS) datasets for 29 modifiable risk factors for iRBD in discovery and replication stages were used. GWAS data for iRBD cases were obtained from the International RBD Study Group. The inverse variance weighted (IVW) method was primarily employed to explore causality, with supplementary analyses used to verify the robustness of IVW findings. Co-localization analysis further substantiated causal associations identified via MR. Genetic correlations between mental illness and iRBD were identified using trait covariance, linkage disequilibrium score regression, and co-localization analyses. Results: Our study revealed causal associations between sun exposure-related factors and iRBD. Utilizing sun protection (odds ratio [OR] = 0.31 [0.14, 0.69], p = 0.004), ease of sunburn (OR = 0.70 [0.57, 0.87], p = 0.001), childhood sunburn occasions (OR = 0.58 [0.39, 0.87], p = 0.008), and phototoxic dermatitis (OR = 0.78 [0.66, 0.92], p = 0.003) decreased iRBD risk. Conversely, a deep skin color increased risk (OR = 1.42 [1.04, 1.93], p = 0.026). Smoking, alcohol consumption, low education levels, and mental illness were not risk factors for iRBD. Anxiety disorders and iRBD were genetically correlated. Conclusion: Our study does not corroborate previous findings that identified smoking, alcohol use, low education, and mental illness as risk factors for iRBD. Moreover, we found that excessive sun exposure elevates iRBD risk. These findings offer new insights for screening high-risk populations and devising preventive measures.

A radiomics-clinical combined nomogram-based on non-enhanced CT for discriminating the risk stratification in GISTs.

PURPOSE: To discriminate the risk stratification in gastrointestinal stromal tumors (GISTs) by preoperatively constructing a model of nonenhanced computed tomography (NECT). METHODS: A total of 111 GISTs patients (77 in the training group and 34 in the validation Group) from two hospitals between 2015 and 2022 were collected retrospectively. One thousand and thirty-seven radiomics features were extracted from non-contract CT images, and the optimal radiomics signature was determined by univariate analysis and LASSO regression. The radiomics model was developed and validated from the ten optimal radiomics features by three methods. Covariates (clinical features, CT findings, and immunohistochemical characteristics) were collected to establish the clinical model, and both the radiomics features and the covariates were used to build the combined model. The effectiveness of the three models was evaluated by the Delong test. RESULTS: The experimental results showed that the clinical models (75.3%, 70.6%), the radiomics models (79.2%, 79.4%) and the combined models (81.8%, 82.4%) all had high accuracy in predicting the pathological risk of GIST in both training and validation groups. The AUC values of the combined models were significantly higher in both the training groups (0.921 vs 0.822, p= 0.032) and the validation groups (0.913 vs 0.792, p= 0.019) than that of the clinical models. According to the calibration curve, the combined model nomogram is clinically useful. CONCLUSIONS: The clinical-radiomics combined model and based on NECT performed well in discriminating the risk stratification in GISTs. As a quantitative technique, radiomics is capable of predicting the malignant potential and guiding treatment preoperatively.

Plasma Soluble Podoplanin as a Biomarker of Hypercoagulability and Cellular Immunity Status in Patients With Non-small Cell Lung Cancer.

Podoplanin (PDPN) is known to play a role in thrombosis, metastasis of tumor cells, the epithelial-mesenchymal transition (EMT), and immune response. The present study aim to evaluate the clinical significance of soluble PDPN (sPDPN) in hypercoagulability and cellular immune status in patients with non-small cell lung cancer (NSCLC). Enzyme-linked immunosorbent assay (ELISA) was used to determine plasma sPDPN levels, and T-lymphocyte distribution was determined using flow cytometry. The levels of sPDPN were markedly higher in the NSCLC group than control group, and sPDPN was higher in patients with advanced-stage and with distant metastases. The high-sPDPN group had lower absolute numbers of CD3+, CD4+, and CD4+/CD8+ ratio than low-sPDPN group. Correlation analysis indicated that sPDPN was positively linked to platelet (r = 0.50, P < .001), D-dimer (r = 0.52, P < .001), and fibrinogen (r = 0.37, P < .001); and inversely correlated with CD3+ (r = -0.37, P < .001), CD4+ (r = -0.44, P < .001), and CD4+/CD8+ (r = -0.37, P < .001). Multivariate logistic regression analysis indicated that sPDPN (odds ratio [OR] = 2.293; 95% CI, 1.559-3.373) and tumor stage (OR = 15.857; 95% CI, 1.484-169.401) were separate risk indicators for hypercoagulability. The receiver operating characteristic curves (ROC) indicated that sPDPN had high diagnostic values for hypercoagulability in NSCLC patients. In conclusion, plasma sPDPN was not only linked to hypercoagulability, but it may also be an indicator of the body's cellular immune status in NSCLC patients.

Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid ß-Oxidation.

Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long-term prognosis in these patients. The CD96+ cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell-intrinsic CD96 enhances the chemotherapeutic response in a patient-derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid ß-oxidation via the CD155-CD96-Src-Stat3-Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell-intrinsic CD96 and an attractive target in improving the chemotherapeutic response.

VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis.

Leptomeningeal metastasis is associated with dismal prognosis and has few treatment options. However, very little is known about the immune response to leptomeningeal metastasis. Here, by establishing an immunocompetent mouse model of breast cancer leptomeningeal metastasis, we found that tumor-specific CD8+ T cells were generated in deep cervical lymph nodes (dCLNs) and played an important role in controlling leptomeningeal metastasis. Mechanistically, T cells in dCLNs displayed a senescence phenotype and their recruitment was impaired in mice bearing cancer cells that preferentially colonized in leptomeningeal space. Upregulation of p53 suppressed the transcription of VLA-4 in senescent dCLN T cells and consequently inhibited their migration to the leptomeningeal compartment. Clinically, CD8+ T cells from the cerebrospinal fluid of patients with leptomeningeal metastasis exhibited senescence and VLA-4 downregulation. Collectively, our findings demonstrated that CD8+ T cell immunosenescence drives leptomeningeal metastasis.

CD16+ fibroblasts foster a trastuzumab-refractory microenvironment that is reversed by VAV2 inhibition.

The leukocyte Fcγ receptor (FcγR)-mediated response is important for the efficacy of therapeutic antibodies; however, little is known about the role of FcγRs in other cell types. Here we identify a subset of fibroblasts in human breast cancer that express CD16 (FcγRIII). An abundance of these cells in HER2+ breast cancer patients is associated with poor prognosis and response to trastuzumab. Functionally, upon trastuzumab stimulation, CD16+ fibroblasts reduce drug delivery by enhancing extracellular matrix stiffness. Interaction between trastuzumab and CD16 activates the intracellular SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A pathway, leading to elevated contractile force and matrix production. Targeting of a Rho family guanine nucleotide exchange factor, VAV2, which is indispensable for the function of CD16 in fibroblasts rather than leukocytes, reverses desmoplasia provoked by CD16+ fibroblasts. Collectively, our study reveals a role for the fibroblast FcγR in drug resistance, and suggests that VAV2 is an attractive target to augment the effects of antibody treatments.

Negative air ions through the action of antioxidation, anti-inflammation, anti-apoptosis and angiogenesis ameliorate lipopolysaccharide induced acute lung injury and promote diabetic wound healing in rat.

Negative air ions (NAIs) being bioactive and negative charged molecules may confer antioxidant and anti-inflammatory activity. We assessed the effect of NAIs on two inflammatory diseases in animal models including lipopolysaccharide (LPS) induced acute lung injury (ALI) and wound healing in diabetic rats. We used intra-tracheal infusion of LPS to induce ALI and made a full-thickness cutaneous wound in streptozotocin-induced diabetic female Wistar rats. We evaluated NAIs effects on reactive oxygen species amount, leukocyte infiltration, wound healing rate, western blot, and immunohistochemistry in the lungs of ALI and skin sections of wounds. Our data found NAIs exposed saline displayed higher antioxidant activity vs. non-exposed saline. NAIs exposure did not significantly affect arterial blood pressure and respiratory frequency in control and LPS treated groups. LPS increased leukocyte infiltration, caspase 3/Poly-ADP-ribose-polymerase-mediated apoptosis formation and decreased Beclin-1/LC3-II-mediated autophagy in lungs. NAIs exposure conferred pulmonary protection by depressed leukocyte infiltration and caspase 3/Poly-ADP-ribose-polymerase mediated apoptosis and enhanced LC3-II-mediated autophagy in LPS induced ALI. NAIs treatment resulted in a significantly accelerated wound closure rate, decreased erythrocyte accumulation and leukocyte infiltration mediated oxidative stress and inflammation, and upregulated expression of skin collagen, vascular endothelial growth factor receptor-2 (VEGFR-2) and factor transforming growth factor-beta 1 (TGF-ß1) vs non-treated group. Based on these results, it is suggested that NAIs conferred a protection through the upregulating LC3-II-dependent autophagy mechanism and downregulating leukocyte infiltration mediated inflammation and caspase 3/Poly-ADP-ribose-polymerase signaling in the LPS-treated ALI and promoted diabetic wound healing through the enhancing skin collagen synthesis, VEGFR-2 and TGF-ß1 pathways.

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and ß-hCG in China: a multicentre, observational, case-control study.

BACKGROUND: Endocannabinoid anandamide (AEA), progesterone (P4) and ß-human chorionic gonadotrophin (ß-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk. METHODS: This is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and ß-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision. RESULTS: The median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage. CONCLUSIONS: The LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and ß-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Tumor cells resistant to phagocytosis inhibit mitochondrial fission of macrophages by overexpressing glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which can be targeted to improve antibody efficacy. Mechanistically, increased cytosolic calcium by mitochondrial fission abrogates the phase transition of the Wiskott-Aldrich syndrome protein (WASP)-Wiskott-Aldrich syndrome interacting protein (WIP) complex and enables protein kinase C-θ (PKC-θ) to phosphorylate WIP during phagocytosis. GFPT2-mediated excessive use of glutamine by tumor cells impairs mitochondrial fission and prevents access of PKC-θ to compartmentalized WIP in macrophages. Our data suggest that mitochondrial dynamics dictate the phase transition of the phagocytic machinery and identify GFPT2 as a potential target to improve antibody therapy.

HMGB1 Mediated Inflammation and Autophagy Contribute to Endometriosis.

Aim: High mobility group box (HMGB)-1 has been implicated in endometriosis due to the important regulatory roles of inflammation in endometriosis. The aim of the present study was to explore the roles of HMGB-1 in endometriosis and to elucidate the underlying mechanism. Methods: Endometrial specimens were collected from women with endometriosis and healthy volunteers. Immunohistochemistry staining was used to determine the expression patterns and localization of HMGB-1 in the normal, eutopic and ectopic endometrial tissues. Western blotting and qRT-PCR were used to determine the mRNA and protein levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1ß], autophagy-related markers [beclin-1, autophagy-related (atg)13, microtubule-associated protein light chain (LC)3-I, LC-II and p62] and HMGB-1, respectively. Spearman's rank correlation analysis was employed to investigate the correlation between HMGB-1 with inflammatory cytokines and beclin-1. Besides, human endometrial stromal cells (HESCs) were isolated from ectopic endometrium and subsequently transfected with shRNA against HMGB-1. After the transfected cells were subjected to hypoxia, ELISA was used to determine the levels of HMGB-1 and inflammatory cytokines in the cell supernatant. Western blotting was used to determine the expression levels of autophagy-related markers in the cells. Results: Positive correlations were observed between HMGB-1 and the inflammatory cytokines. In addition, a positive correlation was also identified between HMGB-1 and beclin-1 in the ectopic endometrium. Further results demonstrated that autophagy-related markers beclin-1, atg13 and p62 were significantly upregulated in the ectopic endometrium. In addition, HMGB-1 knockdown suppressed the levels of inflammatory cytokines IL-6, TNF-α and IL-1ß and autophagy-related markers beclin-1 and atg13, while upregulated p62 in HESCs under hypoxic condition. Conclusion: Knockdown of HMGB-1 under hypoxic condition regulated inflammatory cytokines and autophagy-related markers. HMGB-1 might contribute to the development of endometriosis in part through regulating inflammatory response and autophagy.

Crocin exhibits an antihypertensive effect in a rat model of gestational hypertension and activates the Nrf-2/HO-1 signaling pathway.

Gestational hypertension is a leading cause of both prenatal and maternal mortality and morbidity; however, there have been rather limited advances in the management of gestational hypertension in recent years. There has been evidence supporting the antihypertensive properties of crocin, but the specific mechanism is still unclear. N-Nitro-L-arginine methyl ester (L-NAME) was employed to establish a rat model with a preeclampsia-like phenotype, particularly gestational hypertension. Enzyme-linked immunosorbent assays were conducted to determine the levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1); the levels of the circulating cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α; and oxidative stress factors. Quantitative RT-PCR assays were performed to assess the transcript levels of various cytokines in the placenta, and western blot assays were carried out to evaluate the protein levels of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2-like 2 (Nrf-2). Treatment with crocin reduced the blood pressure of rats with gestational hypertension, which was accompanied by suppressed circulating levels of PlGF and sFlt-1. Crocin further alleviated the inflammatory signals and oxidative stress in the serum, as well as in placental tissues, in rats with L-NAME-induced hypertension. Crocin treatment also improved pregnancy outcomes in terms of fetal survival, fetal weight, and the fetal/placental weight ratio. Finally, in hypertension elicited by L-NAME, crocin stimulated the placental Nrf-2/HO-1 pathway. Crocin alleviated inflammatory and oxidative stress in placental tissues, thereby protecting against gestational hypertension, one of the major phenotypes of preeclampsia, and activated the Nrf-2/HO-1 pathway.

Therapeutic potential of targeting MKK3-p38 axis with Capsaicin for Nasopharyngeal Carcinoma.

Background: Capsaicin is an active compound found in plants of the Capsicum genus; it has a range of therapeutic benefits, including anti-tumor effects. Here we aimed to delineate the inhibitory effects of capsaicin on nasopharyngeal carcinoma (NPC). Methods: The anti-cancer effects of capsaicin were confirmed in NPC cell lines and xenograft mouse models, using CCK-8, clonogenic, wound-healing, transwell migration and invasion assays. Co-immunoprecipitation, western blotting and pull-down assays were used to determine the effects of capsaicin on the MKK3-p38 axis. Cell proliferation and EMT marker expression were monitored in MKK3 knockdown (KD) or over-expression NPC cell lines treated with or without capsaicin. Finally, immunohistochemistry was performed on NPC specimens from NPC patients (n = 132) and the clinical relevance was analyzed. Results: Capsaicin inhibited cell proliferation, mobility and promoted apoptosis in NPC cells. Then we found that capsaicin directly targets p38 for dephosphorylation. As such, MKK3-induced p38 activation was inhibited by capsaicin. Furthermore, we found that capsaicin-induced inhibition of cell motility was mediated by fucokinase. Xenograft models demonstrated the inhibitory effects of capsaicin treatment on NPC tumor growth in vivo, and analysis of clinical NPC samples confirmed that MKK3 phosphorylation was associated with NPC tumor growth and lymphoid node metastasis. Conclusions: The MKK3-p38 axis represents a potential therapeutic target for capsaicin. MKK3 phosphorylation might serve as a biomarker to identify NPC patients most likely to benefit from adjunctive capsaicin treatment.

Emergence Delirium in Elderly Patients as a Potential Predictor of Subsequent Postoperative Delirium: A Descriptive Correlational Study.

PURPOSE: This study aimed to investigate the incidence of emergence delirium (ED) in elderly patients under general anesthesia and to determine the correlation between ED and delirium at five subsequent postoperative days. DESIGN: This research is a descriptive correlational study. METHODS: A total of 168 aged patients undergoing elective general anesthesia were recruited from a comprehensive tertiary teaching hospital with 2,400 beds in Southern China from April 2018 to September 2018. The Nursing Delirium Screening Scale was used to assess delirium at 30 and 60 minutes after extubation or on discharge from the postanesthesia care unit. Patients were assessed for delirium at postoperative days one through five using the same method. Patients' demographic information, including cognitive function, were collected. FINDINGS: Among the 168 aged patients, 58 suffered from ED (34.5%), including the 79.3% for the 46 patients who experienced postoperative delirium (POD). A positive correlation existed between ED and POD (χ2 = 111.744; P < .01). Logistic regression analysis included seven variables: age, preoperative Mini-Mental State Examination score, underlying diseases, American Society of Anesthesiologists grade, surgery duration, postoperative complications, and the presence of ED. Age and ED were concluded to be independent predictive factors of POD. CONCLUSIONS: ED in the first hour after tracheal tube removal is a predictor of delirium at five subsequent postoperative days. Accurate and timely assessment of recovery period can effectively guide the treatment and rehabilitation of POD and maximize prevention of adverse consequences.

[High expression of STAT2 in ovarian cancer and its effect on metastasis of ovarian cancer cells].

OBJECTIVE: To investigate the expression of signal transduction and activator of transcription 2 (STAT2) in ovarian cancer and its correlation with the prognosis of ovarian cancer patients and explore the role of STAT2 inregulating metastasis of ovarian cancer cells. METHODS: RT-qPCR was performed to detect the expression of STAT2 mRNA in 62 fresh frozen ovarian cancer tissues and 62 normal ovarian tissues; immunohistochemistry was used to detect STAT2 protein expressions in 95 paraffin-embedded ovarian cancer samples and 33 normal ovarian tissues. Kaplan-Meier method was used to analyze the correlation between the expression of STAT2 and the prognosis of the patients. We also examined the relationship between STAT2 and the patients' prognosis by analyzing the data in Kaplan-Meier Plotter database. Western blotting was performed to detect the expression of STAT2 in different ovarian cancer cell lines. In A2780 cells with the highest STAT2 expression, we examined the effects of STAT2 interference on cell migration and invasiveness using Transwell migration assay and on the expressions of the downstream molecule epidermal growth factor receptor (EGFR). RESULTS: Ovarian cancer tissues expressed significantly higher levels of STAT2 mRNA than normal ovarian tissue. A high STAT2 mRNA expression was correlated with an advanced FIGO stage. Immunohistochemistry showed that 67.4% of the ovarian cancer samples, as compared with 28.3% of normal ovarian tissues, showed high STAT2 expressions. In ovarian cancer patients, a high expression of STAT2 protein was associated with ascites volume, distant metastasis and FIGO stage (P < 0.05). Survival analysis showed that ovarian cancer patients with a high expression of STAT2 protein had poor overall survival (P=0.021) and progression-free survival (P=0.018). STAT2 was overexpressed in all the ovarian cancer cell lines tested, and A2780 cell lines showed the highest expression. Interference of STAT2 significantly suppressed the migration and invasiveness (P < 0.01) and lowered the expression level of EGFR in A2780 cells. CONCLUSIONS: STAT2 is overexpressed in ovarian cancer. A high expression of STAT2 is associated with a poor prognosis of ovarian cancer patients. STAT2 may promote the metastasis of ovarian cancer by enhancing the expression of EGFR.

Increased PD-1+Tim-3+ exhausted T cells in bone marrow may influence the clinical outcome of patients with AML.

BACKGROUND: Altered expression of T cell immune inhibitory receptors may result in immunosuppression and associate with the poor prognosis of leukemia patients in which the leukemic bone marrow (BM) microenvironment may contribute to such immunosuppression. We found higher numbers of programmed death-1 (PD-1) + exhausted T cells in peripheral blood (PB) from acute myeloid leukemia (AML) patients. To investigate the leukemic BM influence on immunosuppression, we further compared the distributions of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) and the exhausted T cell phenotype in PB and BM from AML patients and characterized their relationship with clinical outcome. METHODS: PB and BM samples from 15 patients with newly diagnosed AML were collected and analyzed for the expression of PD-1, Tim-3, CD244, and CD57 on CD3+, CD4+, and CD8+ T cells by multicolor flow cytometry. RESULTS: The proportions of PD-1 + CD3+ and PD-1 + CD8+ T cells were significantly higher in BM compared with PB. Similarly, higher PD-1 + CD244 + CD3+ and PD-1 + CD244 + CD8+ T cells were found in BM, and an increased tendency for PD-1 + CD244 + CD4+ T cells was also detected in this group. In contrast, increased Tim-3 + CD4+/Tim-3 + CD244 + CD4+ T cells were predominant in BM compared with PB, but there was no statistically significant difference in Tim-3 + CD8+ T cells. Moreover, PD-1 and Tim-3 double-positive CD3+/CD4+/CD8+ T cells were significantly increased in the BM group. In addition, a higher proportion of PD-1 + Tim-3 + CD3+ T cells in the BM and PD-1 + Tim-3 + CD4+ T cells in PB was detected in non-complete remission (NCR) compared with complete remission (CR) patients after first-cycle chemotherapy. CONCLUSIONS: Upregulation of PD-1 and Tim-3 and the exhausted phenotype of CD4+ and CD8+ T cells in the BM of AML patients may contribute to mediating the leukemic immunosuppressive microenvironment, and increased PD-1 + Tim-3+ CD8+ T cells may be related to T cell dysfunction in AML, which may influence clinical outcome.

Increasing Tim-3+CD244+, Tim-3+CD57+, and Tim-3+PD-1+ T cells in patients with acute myeloid leukemia.

AIM: To characterize the distribution of T cell immunoglobulin mucin-domain-containing-3 (Tim-3) within the exhausted T cells in patients with newly diagnosed acute myeloid leukemia (AML) and AML in complete remission. METHODS: Tim-3 expression and coexpression with PD-1, CD244, and CD57 in CD3+, CD4+, and CD8+T cells were analyzed by multicolored fluorescent flow cytometry in peripheral blood from 28 newly diagnosed, untreated AML patient and 12 cases with AML in complete remission, 23 healthy individuals served as control. RESULTS: Increasing Tim-3+CD244+ and Tim-3+CD57+ in CD3+, CD4+, and CD8+ T cells were found in AML and AML-CR groups in comparison with healthy controls. Similarly, increasing Tim-3 coexpression PD-1+ CD3+/CD4+/CD8+ T cells were found in AML group. A high tendency of PD-1+Tim-3+CD3+/CD4+/CD8+ T cells was detected in the AML-M4 subtype group followed by the M2 group, and a low tendency was found in the M3 group. Moreover, Tim-3+CD244+CD8+ T cells were found to be significantly higher in the M4 than that in M3 group. Dynamic changes of Tim-3+ T cells in AML patients who achieved CR after chemotherapy at different time points showed that Tim-3+ T cell subsets were evidently decreased; however, they remained at a higher level in most AML-CR patients. CONCLUSION: We made a novel observation on distribution of Tim-3+CD244+, Tim-3+CD57+, and Tim-3+PD-1+ T cells in patients with AML. Chemotherapy is incapable of resolving immunosuppression in some cases with AML in CR status.

Application of capsaicin as a potential new therapeutic drug in human cancers.

WHAT IS KNOWN AND OBJECTIVE: Capsaicin, the major active ingredient of chili pepper, may play a "dual role" in tumourigenesis, acting as a carcinogen or as a cancer preventive agent. The aim of this study was to investigate the anticancer mechanisms of capsaicin and the effects of capsaicin on traditional chemotherapeutic drugs and radiotherapy in various cancer types and the potential for clinical application in cancer therapy. METHODS: We conducted extensive literature searches through PubMed to collect representative studies of capsaicin in different cancer types. These studies investigated the anticancer molecular mechanisms of capsaicin. We then searched for the effects of capsaicin on traditional chemotherapeutic drugs or radiotherapy. Finally, in terms of clinical application, we searched for the advances of capsaicin-loaded nanoparticles in malignant tumours. RESULTS AND DISCUSSION: In most studies, capsaicin is a potential anti-tumour compound and the anti-cancer mechanisms are mainly related to anti-proliferation, induction of apoptosis and autophagy, anti-angiogenesis and anti-metastasis. It is worth noting that the biological functions of capsaicin are greatly affected by its concentration and the effective concentration in different malignant tumours varies considerably. Furthermore, capsaicin can affect the anti-cancer activity of conventional chemotherapeutic drugs or radiation therapy and more and more capsaicin-loaded nanoparticles have been developed to prolong the drug retention of capsaicin in the blood circulation and allow active targeting of specific cancer cells to enhance its accurate delivery and targeting specificity, suggesting that capsaicin may be used as a potential chemopreventive or a new auxiliary therapeutic drug for cancer. However, there is still a need for well-controlled studies to assess the safety and efficacy of capsaicin, and further preclinical and clinical trials are needed to elucidate its anti-tumour effects when combined with other standard drugs or radiotherapy. WHAT IS NEW AND CONCLUSION: Capsaicin exhibits strong anti-cancer properties in various cancer types. The combination of capsaicin with conventional chemotherapy drugs or radiotherapy can improve the sensitivity, reduce the side effects and enhance the tolerance of patients to cancer treatment. The development of capsaicin-loaded nanoparticles may provide a very promising approach to chemotherapy for malignant tumours.

Higher frequency of the CTLA-4+ LAG-3+ T-cell subset in patients with newly diagnosed acute myeloid leukemia.

AIM: Immune suppression based on alternative regulation of immune checkpoint proteins, for example, programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), which results in T-cell exhaustion, contributes to cancer development and progression. In this study, we sought to characterize the distribution of CTLA-4 and T-cell lymphocyte activation gene-3 (LAG-3) expression on exhausted T cells in different T-cell subsets from patients with acute myeloid leukemia (AML). METHODS: The coexpression of CTLA-4 and LAG-3 on exhausted CD244+ and CD57+ T cells from the CD3+ , CD4+ , and CD8+ T-cell subsets in peripheral blood from 12 patients with newly diagnosed AML was analyzed by multicolor flow cytometry assay. RESULTS: A significantly higher percentage of CTLA-4+ CD3+ , CD4+ and CD8+ T cells was found in patients with AML. In addition, higher numbers of both CTLA-4+ CD244+ and CTLA-4+ CD57+ CD3+ T cells were detected. Interestingly, the increased CTLA-4+ CD244+ T cells were predominantly CD4+ T cells. In contrast, the increased CTLA-4+ CD57+ T cells primarily consisted of the CD8+ T-cell subset. A high proportion of LAG-3+ T cells was found in only a few cases with AML; however, a significantly higher proportion of coexpression of CTLA-4 and LAG-3 in the CD3+ and CD8+ T-cell subsets was detected. CONCLUSION: We for the first time observed higher CTLA-4+ CD244+ CD4+ , CTLA-4+ CD57+ CD8+ , CTLA-4+ LAG-3+ CD3+ and CTLA-4+ LAG-3+ CD8+ T cells in patients with AML, whereas the upregulated expression of LAG-3 on T cells was only found in a subset of the cases. These data may provide further information by complementing the heterogeneity of immune checkpoints expression in AML.