Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

Multidimensional fatigue in Chinese patients with newly diagnosed meningiomas: Prevalence, severity and associated factors.

OBJECTIVE: The purpose of this study was to explore the prevalence, severity, and factors associated with multidimensional fatigue in Chinese patients with newly diagnosed meningiomas. METHODS: This cross-sectional study included 120 Chinese meningioma patients. Data were collected before surgery, including demographic, clinical, psychological, and sleep characteristics, as well as fatigue scores based on completion of the Multidimensional Fatigue Inventory (MFI-20). Mann-Whitney U tests, Kruskal-Wallis H tests, Spearman correlation and multiple linear regression were used to analyze the data. RESULTS: The results showed there was a high prevalence of severe fatigue for each dimension: general fatigue (33.3%), physical fatigue (27.5%), reduced activity (28.3%), reduced motivation (12.5%), mental fatigue (11.7%), and total fatigue (23.3%). Headache and anxiety were found to be associated with general fatigue. Depression was related with physical fatigue. The Karnofsky Performance Status (KPS) score and depression were associated with reduced activity. Depression and the Epworth Sleepiness Scale (ESS) score were correlated with reduced motivation, while the KPS score and anxiety were associated with mental fatigue. Importantly, comorbidity, the KPS score, headache, depression, sleep disturbances, and the ESS score remained strong correlates of total fatigue. CONCLUSIONS: Our findings indicate that newly diagnosed meningioma patients are affected by multidimensional fatigue. For patients with risk factors of fatigue, targeted interventions are advised to decrease fatigue and improve HRQoL.

Active Alignment of Large-Aperture Space Telescopes for Optimal Ellipticity Performance.

Ellipticity performance of space telescopes is important for exploration of dark matter. However, traditional on-orbit active optical alignment of space telescopes often takes "minimum wavefront error across the field of view" as the correction goal, and the ellipticity performance after correcting the wave aberration is not optimal. This paper proposes an active optical alignment strategy to achieve optimal ellipticity performance. Based on the framework of nodal aberration theory (NAT), the aberration field distribution corresponding to the optimal full field-of-view ellipticity is determined using global optimization. The degrees of freedom (DOFs) of the secondary mirror and the folded flat mirror are taken as the compensation DOFs to achieve the optimal ellipticity performance. Some valuable insights into aberration field characteristics corresponding to optimal ellipticity performance are presented. This work lays a basis for the correction of ellipticity for complicated optical systems.

Prevalence, correlates, and impact of sleep disturbance in Chinese meningioma patients.

PURPOSE: Sleep disturbance is common in meningioma patients and may lead to disease aggravation and decreases health-related quality of life (HRQoL). However, the sleep quality of meningioma patients newly diagnosed and ready for surgery has not been well clarified in China. This study aims to evaluate the prevalence, correlates, and impact of sleep disturbance among Chinese meningioma patients. METHODS: In this cross-sectional study, meningioma patients were recruited from the Affiliated Hospital of Nantong University from January 2020 to November 2020. A series of questionnaires were applied: the 0-10 Numerical Rating Scale (NRS), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), the Epworth Sleepiness Scale (ESS), the Short-Form 36 (SF-36), the Pittsburgh Sleep Quality Index (PSQI). Independent samples t test, Mann-Whitney U test, chi-square analysis, Pearson/Spearman correlation, and binary logistic regression were used to analyze the data. RESULTS: One hundred meningioma patients completed the questionnaires. Sleep disturbance affected 43% of the meningioma patients and was linked to many concomitant symptoms, such as headache, fatigue, anxiety, and depression. Binary logistic regression indicated that fatigue and headache were independently associated with sleep disturbance of meningioma patients. Meanwhile, severe sleep disturbance led to lower quality of life. CONCLUSIONS: These findings demonstrated that a considerable number of meningioma patients newly diagnosed and ready for surgery suffered from sleep disturbance, potentially contributing to impair HRQoL. Medical personnel should pay more attention to meningioma patients with sleep disturbance and take effective measures to improve sleep quality, with the ultimate goal to improve their HRQoL.

A genetic variant in the promoter of lncRNA MALAT1 is related to susceptibility of ischemic stroke.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases. Particularly in ischemic stroke (IS), the abnormal expression of MALAT1 played important roles including promotion of angiogenesis, inhibition of apoptosis and inflammation and regulation of autophagy. However, the effects of genetic variation (single nucleotide polymorphisms, SNPs) of MALAT1 on IS have rarely been explored. This study aimed to investigate whether SNPs in promoter of MALAT1 were associated with the susceptibility to IS. METHODS: A total of 316 IS patients and 320 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in the promoter of MALAT1 (i.e., rs600231, rs1194338, rs4102217, and rs591291) were genotyped by using a custom-by-design 48-Plex SNPscan kit. RESULTS: The rs1194338 C > A variant in the promoter of MALAT1 was associated with the risk of IS (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417-0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226-0.991, P = 0.047; Dominant model: adjusted OR = 0.596, 95% CI, 0.406-0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487-0.890, P = 0.007). The haplotype analysis showed that rs600231-rs1194338-rs4102217-rs591291 (A-C-G-C) had a 1.3-fold increased risk of IS (95% CI, 1.029-1.644, P = 0.027). Logistic regression analysis identified some independent impact factors for IS including rs1194338 AC/AA, TC, TG, HDL-C, LDL-C, Apo-A1, Apo-B and NEFA (P < 0.05). CONCLUSIONS: These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS.

NF-kappaB-dependent microRNA-425 upregulation promotes gastric cancer cell growth by targeting PTEN upon IL-1ß induction.

Overexpression of the proinflammatory cytokine IL-1ß is associated with diverse diseases, including cancer. Alteration of microRNAs has been observed in cancer cells exposed to proinflammatory cytokines, yet their function in inflammation stress remains elusive. Here, we show that IL-1ß induces the upregulation of miR-425, which negatively regulates phosphatase and tensin homolog expression by targeting its 3' UTR. An increase in miR-425 depends on IL-1ß-induced NF-kappaB activation, which enhances miR-425 gene transcription upon IL-1ß induction. Consequently, repression of phosphatase and tensin homolog by miR-425 promotes gastric cancer cell proliferation, which is required to protect cells from cisplatin-induced apoptosis. Taken together, our data support a critical role for NF-kappaB-dependent upregulation of miR-425, which represents a new pathway for the repression of phosphatase and tensin homolog activation and the promotion of cell survival upon IL-1ß induction.

Quantitative assessment of the influence of prostate stem cell antigen polymorphisms on gastric cancer risk.

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-amino acid protein related to the cell proliferation inhibition and/or cell death induction activity which has attracted considerable attention as a candidate gene for gastric cancer (GC) since it was first identified through genome-wide association approach. Since then, the relationship between PSCA polymorphisms (rs2294008, rs2976392) and GC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 16 studies involving a total of 18,820 cases and 35,756 controls for the two widely studied polymorphisms of PSCA on genetic susceptibility for GC. Overall, the summary odds ratio for GC was 1.46 (95% CI 1.30-1.69, P < 10(-5)) and 1.49 (95% CI 1.22-1.82, P < 10(-4)) for PSCA rs2294008 and rs2976392 polymorphisms, respectively. Meanwhile, haplotype analyses of the two polymorphisms revealed a significant association between the combination of these alleles and GC risk. When stratifying for ethnicity, significantly increased risks were found for rs2294008 and rs2976392 polymorphism among East Asians in all genetic models, while no significant associations were observed for the rs2294008 polymorphism in Caucasians. In the stratified analyses according to histological type, and source of controls, evidence of gene-disease association was still obtained. In addition, our data indicate that rs2294008 of PSCA is involved in GC susceptibility and confer its effect primarily in noncardia tumors (OR = 1.30, 95% CI 1.12-1.53, P < 10(-4)). Our findings demonstrated that rs2294008 and rs2976392 polymorphism of PSCA is a risk-conferring factor associated with increased GC susceptibility, especially in East Asians.

[MiR-425 up-regulation induced by interleukin-1ß promotes the proliferation of gastric cancer cell AGS].

OBJECTIVE: To evaluate the mechanism of interleukin-1 (IL-1) in tumorigenesis. METHODS: The miRNA expression was profiled with the Exiqon miRCURY(TM) LNA Array System. And the miRecords algorithm and luciferase reporter assays were employed for identifying the targets of miR-425. Cell proliferation assay was performed with CCK8. Cell apoptosis assay was performed with flow cytometry. RESULTS: IL-1ß induced the up-regulation of miR-425, a negative expression regulator of phosphatase and tensin homolog (PTEN). An increase in miR-425 depended upon IL-1ß-induced NF-kappaB activation.Repression of PTEN by miR-425 promoted gastric cancer cell proliferation. CONCLUSION: There is a critical role for NF-kappa B-dependent up-regulation of miR-425. And it represents a new pathway for the repression of phosphatase and tensin homolog activation and the promotion of cell survival upon IL-1ß induction.

Case report: A lung squamous cell carcinoma patient with a rare EGFR G719X mutation and high PD-L1 expression showed a good response to anti-PD1 therapy.

Lung cancer treatment has transitioned fully into the era of immunotherapy, yielding substantial improvements in survival rate for patients with advanced non-small cell lung cancer (NSCLC). In this report, we present a case featuring a rare epidermal growth factor receptor (EGFR) mutation accompanied by high programmed death-ligand 1 (PD-L1) expression, demonstrating remarkable therapeutic efficacy through a combination of immunotherapy and chemotherapy. A 77-year-old male with no family history of cancer suffered from upper abdominal pain for more than half months in August 2020 and was diagnosed with stage IV (cT3N3M1c) lung squamous cell carcinoma (LUSC) harboring both a rare EGFR p.G719C mutation and high expression of PD-L1 (tumor proportion score [TPS] = 90%). Treatment with the second-generation targeted therapy drug Afatinib was initiated on September 25, 2020. However, resistance ensued after 1.5 months of treatment. On November 17, 2020, immunotherapy was combined with chemotherapy (Sintilimab + Albumin-bound paclitaxel + Cisplatin), and a CT scan conducted three months later revealed significant tumor regression with a favorable therapeutic effect. Subsequently, the patient received one year of maintenance therapy with Sintilimab, with follow-up CT scans demonstrating subtle tumor shrinkage (stable disease). This case provides evidence for the feasibility and efficacy of immunotherapy combined with chemotherapy in the treatment of EGFR-mutated and PD-L1 highly expressed LUSC.

Single-Cell Profiling of Bone Marrow B Cells and Early B Cell Developmental Disorders Associated With Systemic Lupus Erythematosus.

OBJECTIVE: The peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown. METHODS: We performed single-cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified patients with SLE into two groups: early B cell (Pro-B and Pre-B) normal (EBnor) and EB defective/low (EBlo) groups. RESULTS: The SLE-EBlo group exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE-EBnor group. Moreover, in one patient with SLE who was initially classified in the SLE-EBlo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase. CONCLUSION: In summary, this study suggests that early B cell loss in BM defines a unique pathological state in a subset of patients with SLE that may play an active role in the dysregulated autoimmune responses.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

SVM-Based Model Combining Patients' Reported Outcomes and Lymphocyte Phenotypes of Depression in Systemic Lupus Erythematosus.

BACKGROUND: The incidence of depression in patients with systemic lupus erythematosus (SLE) is high and leads to a lower quality of life than that in undepressed SLE patients and healthy individuals. The causes of SLE depression are still unclear. METHODS: A total of 94 SLE patients were involved in this study. A series of questionnaires (Hospital Depression Scale, Social Support Rate Scale and so on) were applied. Flow cytometry was used to test the different stages and types of T cells and B cells in peripheral blood mononuclear cells. Univariate and multivariate analyses were conducted to explore the key contributors to depression in SLE. Support Vector Machine (SVM) learning was applied to form the prediction model. RESULTS: Depressed SLE patients showed lower objective support, severer fatigue, worse sleep quality and higher percentages of ASC%PBMC, ASC%CD19+, MAIT, TEM%Th, TEMRA%Th, CD45RA+CD27-Th, TEMRA%CD8 than non-depressed patients. A learning-based SVM model combining objective and patient-reported variables showed that fatigue, objective support, ASC%CD19+, TEM%Th and TEMRA%CD8 were the main contributing factors to depression in SLE. With the SVM model, the weight of TEM%Th was 0.17, which is the highest among objective variables, and the weight of fatigue was 0.137, which was the highest among variables of patients' reported outcomes. CONCLUSIONS: Both patient-reported factors and immunological factors could be involved in the occurrence and development of depression in SLE. Scientists can explore the mechanism of depression in SLE or other psychological diseases from the above perspective.

Association between miR-365 polymorphism and ischemic stroke in a Chinese population.

Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.

Oral traditional Chinese medication for adhesive small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) is one of the most common emergent complications of general surgery. Intra-abdominal adhesions are the leading cause of SBO. Because surgery can induce new adhesions, non-operative management is preferred in the absence of signs of peritonitis or strangulation. Oral traditional Chinese herbal medicine has long been used as a non-operative therapy to treat adhesive SBO in China. Many controlled trials have been conducted to investigate its therapeutic value in resolving adhesive SBO. OBJECTIVES: The aim of this review was to assess the efficacy and safety of oral traditional Chinese medicine (TCM) for adhesive small bowel obstruction. SEARCH METHODS: We searched the following databases, without regard to language or publishing restrictions: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure/Chinese Academic Journals full-text Database (CNKI), and VIP (a full-text database of Chinese journals). The searches were conducted in November 2011. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials comparing Chinese medicines administered orally, via the gastric canal, or both with a placebo or conventional therapy in participants diagnosed with adhesive SBO were considered. We also considered trials of TCM (oral administration, gastric tube perfusion, or both) plus conventional therapy compared with conventional therapy alone for patients with adhesive SBO. Studies addressing the safety and efficacy of oral traditional Chinese medicinal agents in the treatment of adhesive SBO were also considered. DATA COLLECTION AND ANALYSIS: Two authors collected the data independently. We assessed the risk of bias according to the following methodological criteria: random sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other sources of bias. Dichotomous data are presented as risk ratios (OR) and 95% confidence intervals (CI); continuous outcomes are presented as mean differences (MD) and 95% CIs. The data analyses were carried out using Review Manager 5.1. For cases in which necessary information was not reported in the paper, we contacted the primary authors for additional information. MAIN RESULTS: Five randomised trials involving 664 participants were analysed. Five different herbal medicines were tested in these trials, including Huo-Xue-Tong-Fu decoction, Xiao-Cheng-Qi-Tang decoction, a combination of Xiao-Cheng-Qi-Tang and Si-Jun-Zi-Tang decoctions, Chang-Nian-Lian-Song-Jie-Tang decoction, and Fufang-Da-Cheng-Qi-Tang decoction. There were variations in the tested herbal compositions and methods of medicine administration. The main outcomes reported in the trials were effects on abdominal pain, abdominal distension, constipation defection, time of first defecation after treatment, and reoperation rate during the course of the disease. Secondary outcomes selected for this review were not available, including complications such as small bowel perfusion (bowel resection, system complications, and other possible complications), length of hospital stay, cost of hospitalisation, and time from admission to surgical intervention. The results of five trials showed that patients receiving TCM combined with conventional therapy seemed to have improved outcomes compared with patients receiving conventional treatment alone (OR 4.24, 95% CI 2.83 to 6.36).However, we cannot conclusively determine the efficacy of TCM in this review due to inadequate reporting, low methodological quality, and the prevalence of various biases in the reviewed studies. Furthermore, because none of the reviewed trials discussed adverse events, we could not evaluate the safety of TCM for adhesive SBO patients. All trials were conducted and published in China. AUTHORS' CONCLUSIONS: Although many studies have assessed the use of TCM products for adhesive SBO, most were excluded from this review due to their methodological limitations. This systematic review did not find sufficient evidence to support the objective efficacy and safety of TCM for patients with adhesive SBO. The positive evidence should be interpreted with caution given the insufficient number of studies with large sample sizes, the absence of well-designed, high-quality trials, and the lack of safety information. Therefore, further studies with larger sample sizes and high-quality, randomised, and controlled trials are necessary to produce more accurate and meaningful data on the efficacy of Chinese herbal medicines for adhesive SBO.

From an identity process theory perspective: a daily investigation of why and when ostracism triggers ingratiation.

Although existing studies suggest the relationship between ostracism and ingratiation, the knowledge about why and when ostracism promotes ingratiatory behaviors remains limited. Drawing from identity process theory, the current study examines the influence of ostracism on ingratiatory behaviors through the mediating role of self-identity threat on a daily timescale and the cross-level moderation of core self-evaluation. Through a diary study of 117 Chinese college students across 14 consecutive days, we found that daily ostracism had a positive indirect effect on daily ingratiatory behaviors through daily self-identity threat. Core self-evaluation of students weakened the indirect effect, such that only students with low core self-evaluation engaged in daily ingratiatory behaviors to cope with self-identity threat from ostracism. More importantly, supplemental analyses suggested that averaged daily ingratiatory behaviors were negatively related to perceived ostracism one week later. We discussed several theoretical and practical implications of these findings and proposed future research directions.

Higher dietary diversity as a protective factor against depression among older adults in China: a cross-sectional study.

BACKGROUND: Evidence suggests that poor mental health (MH) is a risk factor for the health of older adults. Dietary diversity is considered to be related to healthy aging. However, the relationship between diet and MH is still unclear. Therefore, the purpose of this study was to investigate the relationship between dietary diversity score (DDS) and anxiety and depression among centenarians and their offspring and spouses. METHODS: Our study was observational and cross-sectional. The Generalized Anxiety Disorder Scale (GAD-7), the 15-item version of the Geriatric Depression Scale (GDS-15), and the dietary frequency questionnaire were used to measure the status of anxiety, depression, and dietary diversity. Data were analyzed by Student's t-test, χ2 test, Mann-Whitney U test, correlational analysis, and univariate or multivariate logistic regression. RESULTS: Among the 288 older adults, 12.8% reported symptoms of depression, and 8.7% reported anxiety. People with a lower dietary diversity had higher rates of anxiety and depression. After controlling for age, place of residence, economic status, alcohol drinking, and physical activity, a lower DDS was found to be a risk factor for depressive symptoms [odds ratio (OR): 2.237; 95% confidence interval (CI): 1.009-4.959; P=0.048]. DDS was negatively correlated with depression score in older adults (r=-0.224; P<0.001), especially offspring and their spouses (r=-0.275; P<0.001). However, no significant relationship was observed between DDS and anxiety. In addition, eating legumes (OR: 0.415; 95% CI: 0.188-0.920; P=0.030) and nuts (OR: 0.255; 95% CI: 0.116-0.561; P=0.001) at least once a week can act as protective factors for depression. Eating nuts (OR: 0.405; 95% CI: 0.168-0.978; P=0.044) and meat (OR: 0.396, 95% CI: 0.161-0.975; P=0.044) at least once a week can act as protective factors for anxiety. CONCLUSIONS: These results suggest an association between low dietary diversity and a higher incidence of mental disorders. Further, the possibility of reverse causality cannot be ruled out. It is necessary to conduct further prospective studies.

Exosomal microRNA-551b-3p from bone marrow-derived mesenchymal stromal cells inhibits breast cancer progression via regulating TRIM31/Akt signaling.

Mesenchymal stromal cells (MSCs) play an important role in the development of human cancer. Meanwhile, exosomes released by MSCs can mediate cell-cell communication by delivering microRNAs (miRNAs/miRs). Hence, this study aimed to explore the role of bone marrow mesenchymal stromal cell (BMSC)-derived exosomal miR-551b-3p in breast cancer. In this study, we found that upregulation of miR-551b-5p suppressed the proliferation and migration and induced the apoptosis of breast cancer cells via downregulating tripartite motif-containing protein 31 (TRIM31). In addition, miR-551b-5p could be transferred from BMSCs to breast cancer cells via exosomes; BMSC-derived exosomal miR-551b-3p suppressed the proliferation and migration and promoted the apoptosis and oxidative stress of MDA-MB-231 cells via inhibiting TRIM31. Furthermore, a xenograft mouse model was used to explore the role of BMSC-derived exosomal miR-551b-3p in vivo. We found that BMSC-derived exosomal miR-551b-3p inhibited tumor growth in a mouse xenograft model of breast cancer in vivo. Collectively, these findings indicated that BMSC-derived exosomal miR-551b-3p could suppress the development of breast cancer via downregulating TRIM31. Thus, miR-551b-3p could serve as a potential target for the treatment of breast cancer.

Single-Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring.

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

Associated factors with constipation and health-related quality of life in lung cancer patients with platinum-based chemotherapy: A cross-sectional study.

ABSTRACT: The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.

A Functional Polymorphism in HIF-3α Is Related to an Increased Risk of Ischemic Stroke.

Hypoxia-inducible factor-3α (HIF-3α), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF-3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF-3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10-4.44; P = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02-2.97, P = 0.04; A vs G OR = 1.48, 95% CI, 1.05-2.07, P = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases (P < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.