Bioactive Naphthoquinone and Phenazine Analogs from the Endophytic Streptomyces sp. PH9030 as α-Glucosidase Inhibitors.

A talented endophytic Streptomyces sp. PH9030 is derived from the medicinal plant Kadsura coccinea (Lem.) A.C. Smith. The undescribed naphthoquinone naphthgeranine G (5) and seven previously identified compounds, 6-12, were obtained from Streptomyces sp. PH9030. The structure of 5 was identified by comprehensive examination of its HRESIMS, 1D NMR, 2D NMR and ECD data. The inhibitory activities of all the compounds toward α-glucosidase and their antibacterial properties were investigated. The α-glucosidase inhibitory activities of 5, 6, 7 and 9 were reported for the first time, with IC50 values ranging from 66.4 ± 6.7 to 185.9 ± 0.2 µM, as compared with acarbose (IC50 = 671.5 ± 0.2 µM). The molecular docking and molecular dynamics analysis of 5 with α-glucosidase further indicated that it may have a good binding ability with α-glucosidase. Both 9 and 12 exhibited moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration (MIC) values of 16 µg/mL. These results indicate that 5, together with the naphthoquinone scaffold, has the potential to be further developed as a possible inhibitor of α-glucosidase.

SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.

PURPOSE: Hypertensive disorder complicating pregnancy (HDCP) is a serious clinical disorder syndrome during pregnancy. This study aims at finding novel targets for HDCP therapy. METHODS: HDCP-related mRNAs were firstly screened out and subjected to gene enrichment analysis. We chose protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) as the research object. Thirty-nine HDCP patients at 32 to 40 weeks of gestation were selected as the HDCP group, and 39 normal controls who received cesarean section delivery at 37-42 weeks of pregnancy were enrolled in this study. Chorionic villi samples were collected within 30 min of delivery. The apoptosis of isolated placental trophoblasts was monitored to investigate the regulatory role of PRKAA2. RESULTS: PRKAA2 expression was further proven to be enhanced in the placental tissues of HDCP patients compared with that of normal puerpera. Subsequently, the results of flow cytometry analysis and western blot indicated that PRKAA2 overexpression accelerated primary placental cell apoptosis, while its knockdown attenuated cell apoptosis. Mechanistically, we determined that the level of PRKAA2 succinylation was elevated in the placental tissue of HDCP patients. Through in vitro succinylation assay and mutagenesis, we confirmed that sirtuin 5 (SIRT5) interacts with PRKAA2 at K69 and K260 to induce PRKAA2 desuccinylation. SIRT5 regulated primary HDCP cell apoptosis through PRKAA2. Finally, the animal study revealed that PRKAA2 elevates the systolic blood pressure of HDCP rat model. CONCLUSION: Our findings indicated that SIRT5-mediated PRKAA2 succinylation modulates placental cell apoptosis in HDCP, suggesting that PRKAA2 is a potential therapeutic target for HDCP treatment.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies.

Two α-pyrone analogs were isolated from the endophytic fungus Diaporthe sp. CB10100, which is derived from the medicinal plant Sinomenium acutum. These analogs included a new compound, diaporpyrone F (3), and a known compound, diaporpyrone D (4). The structure of 3 was identified by a comprehensive examination of HRESIMS, 1D and 2D NMR spectroscopic data. Bioinformatics analysis revealed that biosynthetic gene clusters for α-pyrone analogs are common in fungi of Diaporthe species. The in vitro α-glucosidase inhibitory activity and antibacterial assay of 4 revealed that it has a 46.40% inhibitory effect on α-glucosidase at 800 µM, while no antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycolicibacterium (Mycobacterium) smegmatis or Klebsiella pneumoniae at 64 µg/mL. Molecular docking and molecular dynamics simulations of 4 with α-glucosidase further suggested that the compounds are potential α-glucosidase inhibitors. Therefore, α-pyrone analogs can be used as lead compounds for α-glucosidase inhibitors in more in-depth studies.

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival.

Background: Epithelial ovarian cancer, primarily serous ovarian cancer (SOC), stands as a predominant cause of cancer-related mortality among women globally, emphasizing the urgent need for comprehensive research into its molecular underpinnings. Within this context, the dual-specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3) has emerged as a potential key player with implications for prognosis and tumor progression. Methods: This study conducted a meticulous retrospective analysis of 254 SOC cases from our medical center to unravel the prognostic significance of DYRK3. Survival analyses underscored DYRK3 as an independent adverse prognostic factor in SOC, with a hazard ratio of 2.60 (95% CI 1.67-4.07, P < 0.001). Experimental investigations involved DYRK3 knockdown in serous ovarian cancer cell lines (CAOV3 and OVCAR-3) through a shRNA strategy, revealing substantial decreases in cell growth and invasion capabilities. Bioinformatics analyses further hinted at DYRK3's involvement in modulating the tumor immune microenvironment. In vivo experiments with DYRK3-knockdown cell lines validated these findings, demonstrating a notable restriction in the growth of ovarian cancer xenografts. Results: Our findings collectively illuminate DYRK3 as a pivotal tumor-promoting oncogene in SOC. Beyond its adverse prognostic implications, DYRK3 knockdown exhibited promising therapeutic potential by impeding cancer progression and potentially influencing the tumor immune microenvironment. Conclusions: This study establishes a compelling foundation for further research into DYRK3's intricate role and therapeutic potential in ovarian cancer treatment. As we unravel the complexities surrounding DYRK3, our work not only contributes to the understanding of SOC pathogenesis but also unveils new prospects for targeted therapeutic interventions, holding promise for improved outcomes in ovarian cancer management.

The Phytochemical Potential for Brain Disease Therapy and the Possible Nanodelivery Solutions for Brain Access.

Plant-derived phytochemicals have gifted humans with vast therapeutic potentials. Yet, the unique features of the blood-brain barrier significantly limit their accession to the target tissue and thus clinical translation in brain disease treatment. Herein, we explore the medicinal outcomes of both the rare examples of phytochemicals that can easily translocate across the blood-brain barrier and most of the phytochemicals that were reported with brain therapeutic effects, but a bizarre amount of dosage is required due to their chemical nature. Lastly, we offer the nanodelivery platform that is capable of optimizing the targeted delivery and application of the non-permeable phytochemicals as well as utilizing the permeable phytochemicals for boosting novel applications of nanodelivery toward brain therapies.

Concurrent Chemoradiotherapy Increases the Levels of Soluble Immune Checkpoint Proteins in Patients with Locally Advanced Cervical Cancer.

Purpose: Concurrent chemoradiotherapy (CCRT) has been widely applied to locally advanced cervical cancer (LACC) patients, inducing the massive release of antigen and systematic immunomodulatory effects. However, its effect on the soluble immune checkpoint proteins (sICPs) remains unclear, which might play a key role in the immune response. Therefore, the current study explored changes in the levels of 16 sICPs in LACC patients during CCRT. Methods: We prospectively enrolled fifty-one LACC patients treated with CCRT and collected patients' blood before, during and after CCRT. The levels of 16 sICPs were measured using the Luminex platform, and the changes were measured using Friedman test with Bonferroni's posttest. One month after CCRT, the tumor response was evaluated according to the RECIST 1.1 guidelines. Results: The levels of soluble T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3) significantly increased during CCRT (P = 0.041), while those of the soluble B and T lymphocyte attenuator (sBTLA), sCD40, soluble glucocorticoid-induced tumor necrosis factor receptor ligand (sGITRL), sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and soluble inducible T-cell costimulator (sICOS) significantly increased after CCRT (all P < 0.05). Other sICPs showed no significant changes throughout the CCRT (all P > 0.05). 41 (80%), 8 (16%), and 2 (4%) patients showed complete response (CR), partial response (PR), and stable disease (SD) after CCRT, respectively. Interestingly, the level of soluble lymphocyte-activation gene 3 (sLAG-3) was significantly higher among the PR/SD patients as compared to the CR after CCRT (P = 0.009). Conclusions: This study revealed that CCRT might elevate the serum levels of sTIM-3, sBTLA, sCD40, sGITRL, sCD80, sCD86, sPD-1, sPD-L1, sCTLA-4, and sICOS in the patients with LACC. The sLAG-3 level was higher in the patients with poor response to CCRT. These findings revealed the dynamic changes in the sICPs levels during CCRT, which might be helpful in designing optimal treatment strategies for LACC patients.

Real-time demonstration of 103.125-Gbps fiber-THz-fiber 2 × 2 MIMO transparent transmission at 360-430 GHz based on photonics.

In this Letter, we experimentally demonstrate the first real-time transparent fiber-THz-fiber 2 × 2 multiple-input multiple-output (MIMO) transmission system with a record line rate of 125.516 Gbps at 360-430 GHz based on photonic remote heterodyning, hybrid optoelectronic down-conversion, and commercial digital coherent modules. The 103.125-Gbps net data rate using dual-polarization quadrature phase-shift keying (DP-QPSK) modulation is successfully transmitted over two spans of 20-km standard single-mode fiber (SSMF) and 60-cm wireless distance under 15% soft-decision forward error correction (SD-FEC) for a pre-FEC bit error ratio (BER) threshold of 1.56 × 10-2 (post-FEC BER < 10-15). The optical signal to noise ratio (OSNR) margin and the stability of the transmission system are extensively investigated. To the best of our knowledge, this is the first time to realize >100-Gbps real-time transparent fiber-THz-fiber link transmission at beyond the 350-GHz band, making it a promising scheme to pave the way towards a practical seamless integration of a fiber-THz-fiber link to the future 6G mobile communication system.

Thymol improves salinity tolerance of tobacco by increasing the sodium ion efflux and enhancing the content of nitric oxide and glutathione.

BACKGROUND AND OBJECTIVE: Salt stress is one of the most important abiotic stresses affecting the yield and quality of tobacco (Nicotiana tabacum). Thymol (a natural medicine) has been widely used in medical research because of its antibacterial and anti-inflammatory activities. However, the influence of thymol on the root growth of tobacco is not fully elucidated. In this study, the regulatory effects of different concentrations of thymol were investigated. METHODOLOGY: Here, histochemical staining and biochemical methods, non-invasive micro-test technology (NMT), and qPCR assay were performed to investigate the effect of thymol and mechanism of it improving salinity tolerance in tobacco seedlings. RESULTS: In this study, our results showed that thymol rescued root growth from salt stress by ameliorating ROS accumulation, lipid peroxidation, and cell death. Furthermore, thymol enhanced contents of NO and GSH to repress ROS accumulation, further protecting the stability of the cell membrane. And, thymol improved Na+ efflux and the expression of SOS1, HKT1, and NHX1, thus protecting the stability of Na+ and K+. CONCLUSION: Our study confirmed the protecting effect of thymol in tobacco under salt stress, and we also identified the mechanism of it, involving dynamic regulation of antioxidant system and the maintenance of Na+ homeostasis. It can be a new method to improve salinity tolerance in plants.

Relationship between serum 25-hydroxyvitamin D and target organ damage in children with essential hypertension.

Researchers have shown that 25-hydroxyvitamin D (25[OH] D), a kind of active vitamin D in the human body, plays a role in cardiovascular disease (CVD). Low serum 25(OH) D levels have been found to be associated with elevated blood pressure (BP) in adults. However, measurement of 25(OH) D in hypertensive children has not been documented. The aim of this study was to investigate the relationship between 25(OH) D and target organ damage (TOD) in children with essential hypertension. We recruited a total of 346 children with essential hypertension and analyzed the correlation between serum 25(OH) D and TOD. Serum 25(OH) D concentration was significantly lower in the TOD than in the no-TOD group (t = 2.416, P = 0.016), as well as significantly lower in the two-organ damage than in the single-organ damage group (t = 3.140, P = 0.002). Pearson's correlation coefficient (PCC) indicated that serum 25(OH) D levels were negatively correlated with left ventricular mass index (LVMI; r = -0.110, P = 0.041) and albuminuria (r = -0.120, P = 0.026). Linear- regression analysis showed that 25(OH) D was a risk factor for left ventricular hypertrophy (LVH; ß ± s.e. =-0.074 ± 0.036; 95% confidence interval [CI], - 0.145 to -0.003; P < 0.001) and renal damage (ß ± s.e.= -0.018 ± 0.008; 95% CI, - 0.035 to -0.002; P = 0.004). In total, our data revealed that serum 25(OH) D was independently associated with hypertensive cardiac and renal damage, meaning that it was a risk factor for LVH and albuminuria in childhood hypertension.

Refractory Kawasaki disease: modified methylprednisolone regimen decreases coronary artery dilatation.

BACKGROUND: The use of corticosteroids in Kawasaki disease (KD) is still controversial. The aim of this study was to investigate the safety and effectiveness of modified methylprednisolone (mPSL) regimen as an initial treatment for refractory KD. METHODS: This is a real-world observational study. We identified refractory KD with a self-developed scoring system. Patients were divided into the intravenous immunoglobulin (IVIG) + mPSL group and the IVIG group. Clinical outcomes and changes in coronary arteries after the treatment during a 12-week period were observed. Propensity-score matching was used to analyze those patients with similar baseline characteristics. RESULTS: Of a total of 168 patients, 104 patients were assigned into the IVIG group and 64 patients into the IVIG + mPSL group. The therapeutic response rate of the IVIG + mPSL group was significantly higher than that of the IVIG group (98.4 vs 76.0%, P < 0.05). The IVIG + mPSL group had a shorter duration of fever and a higher rate of C-reactive protein decline than the IVIG group (1.17 ± 0.64 vs 1.81 ± 1.16 days; 88.1 vs 83.5%; P < 0.05). The luminal diameter and Z-score of the left circumflex coronary artery (LCX) were significantly smaller and lower in the IVIG + mPSL group than that in the IVIG group at weeks 2 and 12. CONCLUSIONS: Modified mPSL regimen has minimal side effects. It might improve the initial response to IVIG and decrease the dilation of LCX for refractory KD. IMPACT: Modified mPSL regimen (2-4 mg/kg/day, divided into 2-3 doses for 3-5 days, then 1 mg/kg/day, once a day for 3-5 days, then oral prednisone was tapered over 3-5 weeks in 5-7 days steps) as an intensive initial treatment can decrease LCX dilation in high-risk IVIG-resistant KD patients. Our self-developed scoring system has been proven validated and can be used to identify high-risk IVIG-resistant KD patients in North China. The present study provides an alternative therapeutic regimen for high-risk refractory KD patients.

Eyelid ptosis and muscle weakness in a child with Kawasaki disease: a case report.

BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis that often occurs in children under 5 years. Ptosis and muscle weakness associated with KD are rarely documented. CASE PRESENTATION: We present a case of KD with eyelid ptosis and muscle weakness in a 3-year-old boy. At admission, grade IV and grade III muscle strength were recorded for upper and lower limbs, respectively. Diminished patellar tendon reflex was noted. Laboratory evaluation showed hypokalemia with the serum potassium concentration of 2.62 mmol/L. Intravenous immunoglobulin (IVIG) and aspirin were initiated immediately accompanied with methylprednisolone for adjunctive therapy. Potassium supplement was administered at the same time, which resulted in the correction of hypokalemia on the 2nd day of admission but no improvement in ptosis and muscle weakness. Neostigmine testing, lumber puncture, electromyography, and cerebral and full spine MRI were performed, which, however, did not find evidence for neural and muscle diseases. On the 5th day, the fever was resolved. On the 6th day, eyelid ptosis disappeared. And on the 14th day, the muscle strength and muscle tension returned to normal, patellar tendon reflex could be drawn out normally, and the boy regained full ambulatory ability. CONCLUSIONS: KD might affect the neural and muscular systems, and KD complicated with eyelid ptosis and muscle weakness is responsive to the standard anti-inflammatory treatment plus adjunctive corticosteroid therapy.

Aspirin-Induced Delayed Urticaria in Children with Kawasaki Disease: A Retrospective Case-Control Study.

BACKGROUND: Aspirin remains a key component of the standard therapy for Kawasaki disease (KD) in children. Although it is well known that aspirin can cause hypersensitivity such as aspirin-induced urticaria (AIU), AIU in children with KD has not been described. METHODS: A retrospective case-control study was conducted to investigate AIU clinical features, biochemical parameters, treatment and outcomes in children with KD. Furthermore, biomarkers for predicting AIU were explored using the receiver operating characteristic (ROC) curve analysis. RESULTS: We identified 46 AIU cases with 22 boys and 24 girls during April 2015-May 2019. Eighty-nine age-matched KD patients without AIU were randomly chosen as controls. The proportions of children with allergy history and aspirin doses administered in the 2 groups were found not to be significantly different. AIU group had substantially higher baseline C-reactive protein and NT-proBNP levels, and increased neutrophil percent. AIU appeared 6.0 (4.0, 8.0) days after aspirin treatment. Aspirin withdrawal and anti-allergic treatment were applied for AIU, and AIU disappeared in 1-3 days. Baseline NT-proBNP predicted AIU with an AUC of 0.70 (95% CI [0.60 to 0.79]) for sensitivity and specificity of 72.1% and 62.5%, respectively, for a cut-off value of 612.9 mg/L. The length of hospital stay for AIU patients was significantly greater compared with controls. CONCLUSION: AIU in KD children is not related to gender or aspirin dose, and those with AIU have more severe inflammation at admission. Aspirin should be withdrawn for AIU management. Baseline NT-proBNP may serve as a valuable biomarker to predict AIU.

Predictive model based on gene and laboratory data for intravenous immunoglobulin resistance in Kawasaki disease in a Chinese population.

BACKGROUND: Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population. METHODS: Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019. RESULTS: Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset. CONCLUSION: Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.

Prognostic value of lymphocyte-to-monocyte ratio and systemic immune-inflammation index in non-small-cell lung cancer patients with brain metastases.

Aim: We aimed to evaluate the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) in patients with brain metastases from non-small-cell lung cancer (NSCLC). Materials & methods: We conducted Kaplan-Meier analysis and multivariable Cox analysis to evaluate the prognostic values of NLR, PLR, LMR and SII. Results: Kaplan-Meier analysis showed that the patients in low LMR, high NLR, PLR and SII groups were associated with shorter overall survival. Multivariable Cox analysis revealed LMR and SII were independent prognostic factors for overall survival (p = 0.002 and p = 0.004, respectively). Conclusion: LMR and SII are of significant values in clinical prognostic evaluation for patients with brain metastases from NSCLC.

The post-treatment neutrophil-to-lymphocyte ratio and changes in this ratio predict survival after treatment of stage III non-small-cell lung cancer with conventionally fractionated radiotherapy.

Aim: To investigate the predictive potential of post-treatment neutrophil-to-lymphocyte ratio (NLR) and changes in this ratio (ΔNLR) for stage III non-small-cell lung cancer (NSCLC) patients who received conventionally fractionated radiotherapy (CFRT). Patients & methods: The data of 168 NSCLC patients treated at the Shandong Cancer Hospital were analyzed retrospectively. The relationship between progression-free survival (PFS), overall survival (OS) and post-treatment NLR and ΔNLR were analyzed using both Kaplan-Meier and Cox regression methods. Results: Kaplan-Meier survival analyses showed that post-treatment NLR and ΔNLR were associated with PFS (p < 0.001) and OS (p < 0.001) after CFRT. Multivariate analyses revealed that ΔNLR was an independent predictor of PFS (p = 0.001) and OS (p = 0.018). Post-treatment NLR can only be used as an independent predictor of PFS (p = 0.040). Conclusion: Our results demonstrated the prognostic value of the ΔNLR in predicting PFS and OS in stage III NSCLC patients undergoing CFRT. However, post-treatment NLR has predictive value only for PFS.

Gene Polymorphism of Aspirin-Induced Urticaria in Children With Kawasaki Disease.

Objective: To investigate the distribution of the single nucleotide polymorphism (SNP) of LTC4S A-444C in children with Kawasaki disease in northern China and determine whether LTC4S A-444C SNP is associated with aspirin-induced urticaria (AIU). Methods: The clinical data of children with Kawasaki disease hospitalized in our center from April 2015 to November 2017 were collected, and fluorescence in situ hybridization was used to detect the LTC4S A-444C. According to the genotype, the subjects were divided into three groups: AA genotypes, AC genotypes, and CC genotypes. The incidence of AIU in the three groups was calculated and the relationship between LTC4S A-444C SNP and AIU was analyzed. Results: (1) A total of 574 children with Kawasaki disease were enrolled in the study. The allele frequencies for A, C were 980 (85.4%), 168 (14.6%). (2) Twenty-five cases of AIU in AA genotypes, with a positive rate of 6%, 11 cases of AIU in AC genotypes, with a positive rate of 7.5%, 2 cases of AIU in CC genotypes, with a positive rate of 18.2%. CC genotypes had higher incidence of AIU than that of AA and AC genotypes. However, there was no significant difference among the three groups (P > 0.05). Conclusion: The proportion of CC genotypes of LTC4S A-444C in children with Kawasaki disease in northern China is lower than that of AA genotypes and AC genotypes, and the incidence of AIU of CC genotypes is higher than that of AC genotypes and AA genotypes.

Prognostic significance of peripheral CD8+CD28+ and CD8+CD28- T cells in advanced non-small cell lung cancer patients treated with chemo(radio)therapy.

BACKGROUND: Noninvasive prognostic biomarkers are needed for advanced non-small cell lung cancer (NSCLC) patients with different histological types to identify cases with poor survival. Here, we investigated the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28- T cells in advanced NSCLC patients treated with chemo(radio)therapy and the impact of histological type on them. METHODS: Of 232 registered advanced NSCLC patients, 101 treatment-naïve individuals were eligible and included in our study. Flow cytometry was used to evaluate CD8+CD28+ T cells, CD8+CD28- T cells, CD4+ CD25hi T cells, B cells, natural killer cells, γδT cells, and natural killer T cells in patients' peripheral blood. RESULTS: The median follow-up time was 13.6 months. Fifty-nine (58.4%) patients died by the end of our study. Fifty-three of the 101 advanced NSCLC cases selected for our study were adenocarcinomas (ADs), and 48 were squamous cell carcinomas (SCCs). Multivariate analyses showed that increased levels of CD8+CD28+ T cells independently predicted favorable overall survival (OS) [hazard ratio (HR): 0.51, 95% confidence interval (CI) 0.30-0.89, P = 0.021] and progression-free survival (PFS) (HR: 0.66, 95% CI 0.37-0.93, P = 0.038) in ADs, but the prediction in SCCs was not statistically significant. In contrast, high levels of CD8+CD28- T cells independently predicted unfavorable OS (HR: 1.41, 95% CI 1.17-3.06, P = 0.035) and PFS (HR: 2.01, 95% CI 1.06-3.85, P = 0.029) in SCCs, but the prediction in ADs was not statistically significant. ADs had higher levels of CD4+CD25hi T cells and CD8+CD28- T cells and lower NK cells (all P < 0.05) than SCCs. CONCLUSIONS: Our findings uncovered the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28- T cells in advanced NSCLC patients treated with chemo(radio)therapy, which could help to identify patients with poor outcomes and refine treatment strategies.

Pretreatment blood biomarkers predict pathologic responses to neo-CRT in patients with locally advanced rectal cancer.

Aim: To evaluate the value of pretreatment blood biomarkers in predicting pathologic responses to neoadjuvant chemoradiotherapy (neo-CRT) in patients with locally advanced rectal cancer. Materials & methods: We conducted logistic regression analysis and receiver operating characteristic to assess the predictive value of blood biomarkers. The outcome was defined by the pathologic complete response and good response. Results: Carcinoembryonic antigen (CEA) (p < 0.001), neutrophil-to-lymphocyte ratio (p = 0.024), platelet-to-lymphocyte ratio (p = 0.006) and lymphocyte-to-monocyte ratio (LMR) (p < 0.001) were significant predictors of pathologic complete response, with area under the curve of 0.785, 0.794, 0.740 and 0.913, respectively; CEA (p = 0.007) and LMR (p < 0.001) correlated significantly with good response, with area under the curve of 0.743 and 0.771, respectively. Conclusion: Lower LMR and higher CEA, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before treatment could predict poorer pathologic response to neo-CRT in patients with locally advanced rectal cancer.

The predictive effect of the systemic immune-inflammation index for patients with small-cell lung cancer.

Aim: The purpose of this study was to investigate the predictive power of the systemic immune inflammation index (SII) based on neutrophil (N), platelet (P) and lymphocyte (L) on the clinical outcomes of patients with SCLC. Patients & methods: Blood samples of 228 patients were obtained 1 week before treatment to measure the SII (SII = P × N/L). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier curves and Cox regression models. Results: Higher SII was associated with poorer OS (p < 0.001) and poorer PFS (p < 0.001). Multivariable analyses further revealed SII as an independent prognostic factor for OS (p < 0.001) and PFS (p < 0.001). Conclusion: Pretreatment SII was a valuable prognostic factor for PFS and OS in SCLC patients.